# data[].attributes.body
National Human Genome Research Institute

# data[].attributes.attachment_link.readable_text
CRISPR. When I first learned about CRISPR about a decade ago, the technology and the future possibilities were just amazing. A few years after that, I had the joy of meeting Dr. Jennifer Doudna at a small meeting at NHGRI, and we knew at that time that we were talking to a future Nobel Prize winner and, indeed, she got that very recently. This class of enzymes from bacteria has many, many uses, and I thought I'd pick one just for its timeliness. It provided the simple method for detection of COVID ribonucleic acid -- or RNA -- without making copies up front or performing gene amplification, or sometimes called PCR. And that's just a nice impactful example of so many places that this discovery has been important.

Mike Smith, Ph.D.

Division of Genome Sciences

# data[].attributes.attachment_link.description
CRISPR. When I first learned about CRISPR about a decade ago, the technology and the future possibilities were just amazing. A few years after that, I had the joy of meeting Dr. Jennifer Doudna at a small meeting at NHGRI, and we knew at that time that we were talking to a future Nobel Prize winner and, indeed, she got that very recently.

# data[].attributes.body
Standard Youtube Licensing - Mayo Clinic

# data[].attributes.body
Article By: Safiya Zaloum

© 2019 Centre of the Cell

# data[].attributes.attachment_link.readable_text
Check out our article on what gene editing and CRISPR are; in this piece we will be exploring some of the issues surrounding these technologies.

As with all new technologies that have potential to have such big impacts on humans, it is important to consider the ethics; whether it is morally right to use this technology in a variety of different circumstances.

Gene editing can be done on any cell in the human body. The cells in your body can be categorised into 2 groups: somatic and germline. Germline cells are cells that contain DNA which will be passed onto the next generation: eggs or sperm. Somatic cells are the rest of your body cells that will not be passed on to any of your future children. Using gene editing in somatic cells is generally agreed to be a positive thing, as it can cure a disease for an individual. This is what the licensed gene editing therapies do.

However, if someone has a genetic disease that can be passed on, you could edit their germline cells to prevent them passing the condition on to any future children. See this diagram showing the inheritance of cystic fibrosis. The inheritance pattern is autosomal recessive, meaning that you need one copy of the faulty gene from each parent to have the disease. If you have only one copy, you are a carrier and will not have any symptoms, and likely unaware that you could be a carrier unless someone in your family has cystic fibrosis. Cystic fibrosis is a single gene disorder which affects a protein, causing the airway to fill with thick and sticky mucus which makes it hard to breathe. It also affects many other systems, including the digestive tract. This condition may be cured by gene editing in the future.

Although ensuring a disease is not passed onto future generations sounds beneficial, this technology is new. Until further research can be done, we do not know about the long-lasting effects or if it has any unintended consequences. You would be modifying the genome of not just one person but many future generations. There is also the issue that you cannot obtain consent from someone who is not born yet, as it is their DNA that is being altered. The counter argument however is that it is unethical not to use a technology to cure life limiting diseases such as cystic fibrosis. Eliminating diseases that severely affect the quality of a person's life from the gene pool is a compelling argument to use gene editing on germline cells, once the technology has been rigorously tested and proven.

Many people are quite worried about using gene editing for non-therapeutic purposes in germline cells; to alter the DNA of a person to change normal human characteristics, for example eye colour or intelligence. You might have heard of 'designer babies'; a concept where the parents can determine the characteristics of their unborn child through gene editing, choosing their height for example. This is likely quite far away in terms of what is possible, as for many superficial or physical traits, it is not known exactly what genes are responsible so it would not be possible to choose these characteristics. However, it is not outside the realms of possibility that in the future, parents wishing to gene edit their embryos to avoid a genetic disease may also want to choose the colour hair of their future child, or give them a faster metabolism. Gene editing opens up the possibility of slowly modifying the gene pool for the whole of humanity; a huge and irreversible change.

Germline cell editing and genome editing in embryos is currently illegal in many countries including Australia, Canada and Europe, due to some of these ethical concerns. However, in China there are only guidelines against it. Reports emerged from China in 2018 of twin girls born whose embryos had been gene edited. The scientist claimed to have disabled the CCR5 gene which enables HIV to enter cells; by doing this he may have helped protect the girls against HIV. However, he faced worldwide backlash and was fired for failing to follow procedures and do adequate safety testing. Read more about this case .

Another concern is access to this technology. Will it be widely available so that anyone can buy a kit and do some genetic modification on themselves or their pet? Or will it be tightly regulated with only a select few having access? There are problems with both scenarios. The general consensus is that everyone should have access to the life-changing disease-eradicating CRISPR therapies. These new therapies coming to market can be extremely expensive. Rules and regulations will be needed to ensure that those who need access have it and to avoid further widening already existing health inequalities.

# data[].attributes.attachment_link.title
What are the ethical considerations for CRISPR and gene editing technology? | Centre of the Cell

# data[].attributes.attachment_link.description
By Safiya Zaloum Check out our article on what gene editing and CRISPR are; in this piece we will be exploring some of the issues surrounding these

# data[].attributes.body
Innovative Genomics Institute

# data[].attributes.attachment_link.readable_text
You may have heard that CRISPR tools can alter disease-causing genes and may be able to treat a variety of disorders. This is true, but CRISPR tools may be able to treat or prevents diseases in many other ways as well! In this section, we dive into the many different ways doctors and researchers can use CRISPR tools to improve human health. Please note that many of the treatments discussed in this section are theoretical and/or currently in development.

Download Graphic Assets (CC BY-NC-SA 4.0)

Origins of genetic disease
CRISPR tools help us study mono- and polygenic diseases

DNA encodes all the proteins that make up our cells. Certain DNA sequence variants encode malfunctioning proteins, or are "broken" so they don't encode a protein at all. These have the potential to cause genetic diseases. There are two main types of genetic disease:

Single gene disorders (monogenic diseases) - These are rare diseases caused by a DNA variant in a single gene or region. Researchers use patient data to identify such variants. These variants are tedious to recreate in lab and test with conventional techniques.

Multi-gene disorders (polygenic diseases) - These more common diseases are caused by combinations of DNA variants. Any one of these variants won't cause disease on its own, but in combination, they can. Environmental and lifestyle factors can play a major role in the development of multi-gene disorders as well. Because of their complex etiology, multi-gene disorders are more difficult to study than single gene disorders.

CRISPR tools make it much easier to study both types of genetic disease.

Genetic diseases

DNA variants lead to disease because they alter cellular functions. S ome DNA variants cause very important cellular parts to malfunction. Other variants encode completely non-functional parts, or are "broken" in a way that stops a protein from being made at all. Some DNA variants are in noncoding regions of DNA that have important functions like controlling gene expression. With such intense impacts, these variants can, on their own, lead to defective cells. When this happens, it results in a single gene disorder.

Think of a cell like a sports team. A DNA variant that causes a monogenic disease is like an injured star player or a benched mediocre player.

Other DNA variants lead to dysfunctions that aren't quite so impactful. These may encode proteins with reduced function. They may also encode nonfunctional versions of less important proteins, or stop a non-essential protein from being made altogether, or impact gene regulation. A cell can compensate for each dysfunction individually, but together the small individual dysfunctions add up to defective cells. When this happens, it results in a multi-gene disorder.

Think about the sports team again. DNA variants that cause multi-gene disorders are like the entire team having a bad game. Normally other team members can compensate if one person is having a bad day, but the team will lose if everyone underperforms. In multi-gene disorders, many genes underperform to cause disease.

It is important to note that disease is often a product of an interaction between DNA variants and lifestyle, life experience, and/or the environment. Sometimes DNA variants encode proteins that malfunction only under certain conditions. Other times, the combination of life style, experience, or environmental factors combine with DNA variants to lead to disease. For example, some people may have a DNA variant that makes them more likely to develop asthma. But, asthma only occurs when people with that variant live in areas with moderate or high air pollution. In this way, the environment has a big impact on whether DNA variants lead to disease.

Further, some health issues are almost entirely due to life style, life experiences, and environment. For example, back problems can result from an occupation involving heaving lifting. There might be some gene variants that make people more or less prone to back issues, but these will generally have little impact compared to a lifetime of heavy lifting.

Using CRISPR genome-editing tools to study genetic diseases

CRISPR genome-editing tools facilitate single and multi-gene disorder research. The first step of this work is for researchers to determine if suspected DNA variants actually cause disease. To do so, they add the variants to healthy cells and remove them from diseased cells. If the variants cause disease, the healthy cells get sick and diseased cells get better.

For single-gene disorders, researchers need to add or subtract just one DNA variant. CRISPR genome-editing tools make this process easier and faster. Using these tools, researchers can test variants in many cells under many conditions. They can quickly learn a lot about these diseases and how they impact cellular function.

CRISPR tools are even more impactful in multi-gene disorders. With multi-gene disorders, researchers must study many DNA variants at once. This was not workable before CRISPR genome editing. CRISPR tools make polygenic disease research possible for two reasons:

1. Researchers simply use many It is easy to direct CRISPR genome-editing tools to many sites -guide RNAs at the same time to direct CRISPR tools to many DNA sequences simultaneously. Before CRISPR tools were available, researchers had to make entire new tools to edit each new site. This was very time consuming and impractical for all the sites in multi-gene disorders.

2. Old genome-editing tools were very large and it was hard to deliver more than one at once. The guide CRISPR genome-editing components are small and easy to deliver - RNAs used in CRISPR genome-editing are small. So, researchers can deliver many at once and theoretically edit all the sites in a multi-gene disorder.

With CRISPR tools, researchers are learning much more about DNA variants and disease. Using this information, they will create new treatments. Some will rely on using the knowledge gained from CRISPR-based research to develop traditional small molecule drugs, antibody-based treatments, and more. Some will use genome editing to directly change disease-causing sequences to healthy versions.

Disease modeling

Learning how to treat diseases in human-relevant models

How scientists study diseases in the lab

Using CRISPR tools to create disease models

To develop new treatments for disease, researchers need ways to test their safety and efficacy before testing them in clinical trials with human patient-volunteers. This is where disease models step in.

Disease models simulate the important characteristics of human diseases. These models can take many forms, from cells in petri dishes to whole animals.

Simulating diseases with CRISPR tools

CRISPR tools help researchers create disease models in two main ways:

1. By enabling researchers to verify that candidate disease-causing DNA sequence variants do indeed cause disease

2. By causing cells or animals to take on disease-like characteristics

For example, pretend you are a researcher studying diabetes. You might identify potential diabetes-causing DNA sequence variants by analyzing DNA from diabetic individuals. To verify that these variants cause disease, you could use CRISPR tools to insert them into pancreas cells grown in a dish. You could then test whether these cells take on characteristics associated with diabetes. For instance, you might test if the cells produce insulin.

Once verified, researchers use DNA sequence variants to simulate diseases in human-relevant models. First they choose appropriate platforms for their disease models. A platform could be cells in a dish, cells grown together into tissues or organ-like structures, or even whole organisms.

The particular characteristics of a disease and the particular experiments need to be considered carefully when choosing a model. For a disease like diabetes that affects the whole body, sometimes a whole organism would be a better choice. A wise choice would be an organism with a pancreas because many of the effects of diabetes operate through the pancreas. A mouse could be a good option.

After carefully choosing a platform, the next step is to simulate the disease in the platform. There are a variety of ways to do this:

Use CRISPR tools to edit DNA sequences in specific cells - For example, researchers could insert diabetes-causing DNA variants into mouse pancreatic cells.

Use CRISPR tools to edit DNA sequences in whole organisms - Here researchers insert disease-causing DNA sequence variants into egg/sperm cells or embryo cells. These cells later give rise to organisms with disease-causing DNA variants in every cell.

Use xenografts - A xenograft consists of tissue transferred from one species to another. Xenografts enable researchers to study diseased human cells in non-humans. Xenografts can come from a variety of sources, including patients or genome-edited cells grown in the lab. For example, researchers can transfer human tumors to mice. Later they can study how the tumors affect the mice. They can also test how drugs delivered to the mice impact the tumors.

Create chimeras - Chimeras are organisms composed of mixtures of cells with different DNA sequences. They might even contain cells from different species. Chimeras can be useful for studying human diseases in non-humans. For example, researchers can create pigs containing human cells in their organs. Such "humanized" organs might better simulate human disease. Researchers use complex genome editing and stem cell-based techniques to create chimeras.

Researchers don't have to use genome editing to create disease models. For example, CRISPR tools that turn up and down genes can also cause disease-like effects. Even chemical treatments can cause disease-like symptoms. Nonetheless, diseases caused by DNA sequence variants are often best modeled using the same variants.

With an appropriate model in hand, researchers can learn a lot about disease biology. They can use models to learn how diseases impact particular organs or tissues. They can also use models to test new treatments. If a treatment is effective in a model, researchers might later test it in humans. Because CRISPR tools make it much easier to make disease models, they help researchers get new treatments to the clinic more quickly!

Genome-editing therapies

How scientists are developing CRISPR-based therapies to treat diseases

Adding or changing DNA to treat disease

Did you know?

*Note*

In 2019, the first individual with a genetic disease - in this case, the blood disorder beta thalassemia - was dosed with a CRISPR-based therapy in a clinical trial. Since then, several more trials have begun in areas ranging from type 1 diabetes, infectious disease, genetic blindness, and more. To learn more about CRISPR-based trials, check out CRISPR Clinical Trials: A 2022 Update
page. If you're interested in learning more about potential treatments or trials for yourself or a loved one, check out our Patients & Families page.

Cell therapy

Vocabulary

Genome editing, cell therapy, in situ genome editing, off-target edits, germline editing, somatic cell, germ cell

In situ genome editing

In genome-editing therapies, scientists deliver helpful DNA sequences to cells. These DNA sequences can play a variety of roles. They might make small edits to DNA to revert to a healthy variant of the DNA sequence or turn a gene "on" or "off." They might replace sections of a DNA sequences that cause disease. They might also give cells new abilities. CRISPR tools make gene therapy easier, but are not the only way to do it.

This article divides genome-editing therapies into three groups. In order of practicality, they are:

Cell therapies* - These use lab-modified cells to treat disease.

In situ genome-editing therapies* - These use genome-editing tools to fix diseased cells in patients. *Both cell and in situ therapies use 'somatic' genome editing. That is, they alter adult cells that cannot give rise to offspring.

Germline therapies - These use genome editing to alter DNA in cells that will form entire organisms (think eggs and sperm). Thus, all cells that make up the resulting organisms have altered DNA. Their future offspring will inherit their altered DNA.

These genomic therapies come with escalating levels of ethical and technical difficulties. The first two types of are already reaching the clinic. Germline therapy requires more research, public discussion, and oversight before it reaches the clinic (if at all).

Germline editing

Cell therapies use modified cells to treat disease. Generally these cells are isolated from a patient or an individual acting as a cell donor, and then genome edited and multiplied in the lab. After editing, doctors deliver these cells (back) to patients, often by IV infusion. Once in the body, the genome-edited cells fight a specific disease.

A CRISPR-based treatment for sickle cell disease, which is being studied in clinical trials, is a great examples of a cellular therapeutic. In sickle cell disease, a faulty form of the protein hemoglobin causes red blood cells to be misshapen, or "sickled." In the treatment, blood stem cells are harvested from an individual, edited in the lab, and then infused back into the patient, where they take up residence in the bone marrow and start making healthy, round red blood cells.

Cell therapies are often more practical than the other forms of genome editing for many reasons:

The genome-editing process is easier - It's less technically challenging to edit cells in the lab than in the body. Scientists also usually have more cells to work with in the lab.

It's easier to edit the specific cell type - When genome-editing tools are in the body, there's a risk of them modifying cell types besides the kind being targeted. If cells are isolated from the patient and modified outside of the body, there is very little risk of editing the wrong cell types.

Modified cells can be easy to deliver to patients - These are generally infused into the bloodstream or delivered to a particular organ.

There is little or no risk of passing on the modified cells to future generations - In this sense, cellular therapeutics are like standard drugs. They only directly impact the individuals they treat. So, they raise fewer ethical issues than the other types of genome editing.

Future cell therapies may cure a variety of diseases. Some scientists are working to modify liver cells to cure blood diseases like hemophilia. Others are working on ways to create pancreas cells to cure diabetes. Still others are working on making immune cells resistant to HIV infection. And researchers are finding new ways to isolate and modify cells all the time.

In situ means "in the original place." In situ therapies treat diseases at their source in defective cells. They use genome editing to alter disease-causing DNA variants in the body.

In situ genome editing is generally more difficult than cell therapy. It is harder to deliver genome-editing tools directly to cells in the human body than to isolated cells in the lab. Most cells are not as easily accessible as those in the eye. Think about how difficult it could be to deliver genome-editing tools to widely distributed cells like muscle cells. Many diseases involve such widely distributed cells.

Even when target cells are accessible, genome editing is challenging because it must be very precise. If genome-editing tools act in the wrong cells, there could be negative health consequences. Researchers can achieve some precision using special in situ viruses. These viruses are themselves modified so they no longer cause disease, but still have their native ability to get into specific kinds of cells. Genome-editing tools can be packaged inside the viruses, who carry them into specific cells. There is always some risk because viruses aren't 100% accurate. Researchers also don't have viruses to target each type of cells.

Although unlikely, gene therapies to minimize the risk of these in situ genome editing could also result in germline editing, causing future generations to inherit DNA alterations made by the genome-editing components . This would happen if genome-editing tools were accidentally delivered to egg or sperm cells. So, researchers must be very careful when developing in situ off-target edits.

Germline editing is highly controversial. It uses genome-editing tools to alter sperm, eggs, or embryos - cells that give rise to whole organisms. As a result, these organisms pass on the changes in their DNA to their offspring generations. In other words, germline editing impacts future generations and not just individual patients. For this reason, it brings up many more ethical questions than cell or in situ editing and is prohibited by many countries. There is currently no country that allows heritable germline genome editing, meaning, changes that would be passed on to generations beyond the initial edited organism.

However, germline editing is worth thinking about because certain diseases could most effectively be treated effectively with germline editing. Diseases caused by DNA variants that alter many cells in the body are a good example. Their health impacts are too broad for cell therapies and in situ gene therapy cannot reach all the defective cells. Germline therapy is also the most effective option for diseases that have effects very early in development. These diseases might be severely disabling or fatal before birth or in infant or toddler years, so preventing them from developing at all is the most effective approach.

Despite these potential uses, there are many reasons germline editing is controversial:

Scientists don't know how to do germline editing safely yet - It's unclear whether current genome-editing techniques are accurate enough for germline therapy. 'Off-target' germline effects or unwanted 'on-target' effects would result in modifications throughout the entire treated organism, potentially resulting in drastic health consequences.
Off-target editing and unwanted on-target effects are possible in the other types of gene therapy, but the risk is less. Scientists edit a limited number of cells in cell and in situ treatments. This lowers their chances for drastic off-target consequences. In cell therapies, scientists can even test their cells for off-target editing. So, they can treat patients using only cells with the correct edits. It is not possible to confirm that an edited embryo has only wanted changes without destroying the embryo.

Germline therapy has the potential to alter the human gene pool - Many people think that permanently altering human genetics is a bad idea. They are concerned that changing the gene pool might have unforeseen negative consequences on future generations. Bolstering this argument, some disease-causing DNA variants have health benefits in particular environments. As such, it may be unwise to take actions that could remove these variants from the gene pool.

Germline therapy could be used for enhancement as opposed to treatment - Here "enhancement" means trying to improve human genetics for reasons beyond treating or preventing disease or disability. For example, parents could use germline editing to give their children bigger muscles. While many human characteristics like intelligence are too complicated for this to be done in the short term and too shaped by environment to be realistic even in the long term, some kinds of enhancements are theoretically possible. Detractors believe that enhancement could exacerbate inequities between classes, races, geographies, and more. Enhancement might be possible to a lesser extent with the other types of genome editing, but those DNA changes wouldn't extend beyond individual patients.

Inherent lack of consent - Germline therapy "treats" germcells that will form fetuses, and ultimately, new individuals. However, these future individuals have no means to consent to the treatment. This is compounded by the fact that germline edits are heritable: as a result, lack of consent extends far beyond the treated individual and into future generations.

These issues are important and societies must consider them before using germline editing. It needs extensive and inclusive discussion, debate, consent, and regulation before it could be used ethically. For now, families with genetic risks have options including carrier screening, embryo screening, and prenatal diagnostics.

Find the Official IGI Stance on Human Germline Editing here.

Delivering CRISPR therapies
Getting CRISPR tools into human cells for genome editing

CRISPR therapies can have profound impacts on disease. Their effectiveness depends on our ability to deliver CRISPR tools to cells. Physicians need ways to distribute CRISPR tools to specific cell types. They also need ways to get these tools across cellular barriers.

Researchers have come up with many ways to get CRISPR tools into cells. Methods for systemic delivery involve broadly distributing CRISPR tools throughout the body, and the delivery tool (discussed in detail below) targets specific cells as it moves through the whole body system. Methods for local delivery get CRISPR tools directly to specific tissues or cells.

Which delivery method a physician uses depends on the specific therapy. With diseases that impact cells throughout the body, systemic delivery is very important. For example, muscle wasting diseases like muscular dystrophy might need systemic delivery. With diseases that impact specific cells or tissues that can be easily accessed, local delivery may be the best option. For example, certain bladder conditions could benefit from local delivery to the bladder. Indeed, local delivery might be a better option in these cases because it can limit side effects and the risk of unwanted edits in other cell types.

We discuss three of the most popular methods for delivering CRISPR therapies below. These have varying levels of potential for systemic and local delivery. Each also has its own pros and cons. Researchers are actively working on improving all these methods and creating new ones.

1. Specialized viruses

Viruses naturally infect human cells. During this process they often release their DNA into the infected cells. Normally , this DNA encodes proteins that force cells to produce more copies of the Ultimately , the viruses sometimes kill the infected cells. virus.

Researchers have discovered ways to domesticate some viruses. The domesticated viruses no longer turn cells into virus-replicating factories. Instead, they carry genome-editing tools and release them into their target cells. Researchers can deliver DNA encoding CRISPR tools into specific cell types using these viruses. Adeno-associated viruses ( AAV) are commonly used for this.

Viruses can deliver CRISPR tools either systemically or locally . Some viruses are great at systemic delivery. Some are more suited for local delivery. Researchers can even modify some viruses to make delivery more or less specific. They are very versatile.

Viruses do have some drawbacks. For example, some can cause powerful immune reactions. Others may insert their CRISPR-encoding DNA into random locations in the genome. Still others can only deliver small pieces of DNA. The first two drawbacks could result in severe health consequences for patients. The third puts limitations on the types of CRISPR tools that can be delivered . However, viruses have a long history in gene therapy and, more recently, in genome editing, so physicians know how to monitor and treat their side-effects.

Viruses can stick around in cells for weeks, months, or years. When viruses are used to deliver genome-editing components, it can result in the presence of genome-editing components for weeks, months, or years. This may be desirable in some cases, but also increases the risk of immune reactions to the virus or the CRISPR proteins, as well as the risk of off-target effects, as opposed to other methods which lead to transient expression of genome-editing components.

2. Nanoparticles

Lipid nanoparticles are small, spherical structures made out of lipids (fats) and may also be referred to as LNPs. Researchers have various ways to encapsulate CRISPR tools inside these structures. They easily pass through membranes and deposit their CRISPR cargoes into cells. Usually the CRISPR tools are encapsulated as mRNA or protein.

LNPs are easy to prepare and researchers can easily modify their structures. Some formulations might better penetrate certain cell types, pass through bodily barriers, or have more stability . Unlike viruses, nanoparticles don't tend to provoke immune responses, so they may have fewer side effects and be more safe than viruses when administered to the body.

LNPs can be used to local delivery. If injected into the bloodstream, these particles accumulate in the liver, making them great for systemic therapies that target the liver. However, they may have low effectiveness when delivered systemically for therapies targeting other cells in the body. Researchers are working on developing nanoparticles that are more versatile for systemic delivery to cells, tissues, or organs besides the liver.

LNPs lead to transient expression of genome-editing components. Within a week or so of administration, there will be no trace of the nanoparticles of genome-editing components. This decreases the risk of immune reactions to the CRISPR proteins, as well as the risk of off-target effects, relative to viral delivery.

3. Direct delivery of naked CRISPR tools

In the above methods, researchers encapsulate CRISPR tools before delivery. In some cases it makes sense to deliver non-encapsulated "naked" CRISPR tools. For example, cell therapies use modified cells to fight disease. These cells are usually modified in the lab and then injected or infused back into patients. In the lab, researchers can add the naked CRISPR tools directly to the growing cells. With the proper mixture of chemicals or electric pulses, these cells can be coaxed to take up the tools.

It's also possible to modify naked CRISPR tools to make cells in the body more likely to take them up. These naked but disguised tools are like trojan horses, and cells will pull these disguised tools into their membranes. Once inside, the tools get to work editing DNA.

Currently it only makes sense to deliver naked CRISPR tools locally . Naked CRISPR tools can provoke immune responses. They're also not stable enough for systemic delivery. Nonetheless, researchers are actively coming up with ways to improve naked delivery. Like nanoparticles, naked CRISPR tools would be present only transiently.

CRISPR delivery options and improvements to come

Researchers are working on ways to improve these delivery methods and develop new methods to get CRISPR tools to the right cells and reduce risks and side effects.

Xenotransplantation

Replacing human organs with animal organs

How CRISPR tools could be used to help replace human organs with animal organs

What is a xenograft?

Every year, thousands of people die waiting for organ transplants because there are just not enough organs available. CRISPR genome-editing tools may be able to ameliorate this problem. Researchers hope to use these tools so we can replace human organs with animals organs. These xenografts could potentially save many human lives.

Making xenografting more workable with CRISPR genome editing

Xenografts are tissues or organs transplanted from one species to another. Xenografts help scientists study human tissues. They can also treat human ailments. For example, doctors can replace human heart valves with pig heart valves. Doctors can also treat burn victims with pig or fish skin grafts.

Replacing whole human organs with xenografts is difficult. The human immune system has many ways to detect and reject non-human cells. Non-human organs can also carry zoonotic diseases which could put patients at risk.

Researchers can use CRISPR genome-editing tools to modify whole animals. Certain modifications could result in making animal organs more amenable to xenografting. Such modifications come in the following forms:

Modifications that delete viral DNA - For example, pigs have viruses hiding in their DNA. In xenografts, these viruses could infect human patients. Researchers have removed many of these viruses from pigs using CRISPR genome editing. So, organs from these pigs should be less dangerous to humans.

Modifications that make the human immune system less likely to attack the xenograft - Some sequences of animal DNA encode proteins recognized by the immune system. Using genome editing, researchers can remove or modify these sequences. They can also use genome editing to give animals DNA sequences that calm down the immune system.

Modifications that "humanize" animal organs - These modifications are controversial. To make them, researchers use genome editing tools to put human DNA into animals. This DNA encodes cellular parts that make animal organs more human-like. In addition, researchers can replace cells in developing animals with human cells. Under the right conditions, the human cells will form entire organs in the animals. These essentially human organs should be easier to transplant.

Since the 1960s, there have been a handful or so of xenotransplantations done without success. In 2022, the first xenotransplantation aided by CRISPR was performed; the patient only survived for two months after the operation. Whether xenografts are adopted more broadly depends not just on improving the protocols, but also on opinions of xenografts by society at large. Societies must weigh the risks and benefits of xenografts, as well as concerns for animal welfare.

Nucleic acid detection

Detecting disease-causing organisms with CRISPR

How CRISPR proteins can be used to detect specific nucleic acid sequences

How do CRISPR nucleic acid detectors work?

Some diagnostic tools detect disease-causing organisms. Doctors use them to discover why people are sick. Others use them to test food and drinking water for microbial contamination.

One way to detect disease-causing organisms is to identify their DNA. Unfortunately, many DNA identification methods are difficult to use. CRISPR DNA detectors may provide a simple alternative: they can be made to light up in the presence of specific DNA sequences.

CRISPR-Based Diagnostic Tools

CRISPR-based DNA detectors have 2 key components:

1. Cas proteins that cut apart RNA or DNA (nucleic acids) in a non-targeted way after cutting a user-specified DNA sequence.

2. Special kinds of nucleic acids that glow when cut.

In DNA detectors, researchers combine these two components with DNA samples. If the user-specified DNA sequence is present, then the following happens:

1. The Cas protein cuts the target DNA sequence.

2. The Cas protein starts to cut apart nucleic acids in a non-targeted way.

3. The Cas protein cuts apart the special nucleic acids.

4. The special nucleic acids glow.

The glowing nucleic acids are easy to see. They effectively tell users that target DNA is present.

CRISPR-based DNA detectors are easy to target to new sequences. Researchers just swap out the guide molecules directing them to their targets. Thus, CRISPR DNA detectors can spot many organisms.

For example, a doctor could use CRISPR-based DNA detectors to diagnose disease. The doctor would create many DNA detectors. Each would glow upon detecting DNA from a different disease-causing organism. The doctor would then add patient samples (e.g. blood) to the detectors. Depending on which detector glowed as a result, the doctor would find out which organism made the patient sick. Then, the doctor could prescribe an appropriate treatment.

This is just one example of a CRISPR-based tool impacting health without genome editing. In general, CRISPR technologies are powerful because of their customizability and ease of use. Hopefully we'll continue to see more creative applications of CRISPR technologies in the future.

Safety concerns for CRISPR therapies

Making sure CRISPR tools do the right thing in the right place at the right time

Off-target editing, immune responses to CRISPR proteins, and unintended effects

Off-target effects

CRISPR therapies have many uses, but all face some common safety risks. Below we discuss some of these risks and ways to mitigate them.

Provoking immune responses

CRISPR tools occasionally make changes at the wrong location in the DNA, usually sequences that are similar to the target DNA sequence. These are known as off-target effects.

Off-target effects could have have drastic consequences. For instance, they might change DNA sequences that control cell growth, making cells cancerous. Other unwanted DNA changes might prevent cells from carrying out important functions. For example, they might prevent pancreas cells from producing insulin.

There are many ways to reduce the risk of off-target effects. You may recall that guide RNAs (gRNAs) target CRISPR tools to specific DNA sequences. Researchers can test many gRNAs to find the most accurate ones. For instance, they can test their gRNAs and CRISPR tools on cells in the lab. Then they can examine the DNA sequences in these cells. If they find a high frequency of off-target effects, they will likely chose to redesign their gRNAs.

Researchers have also modified CRISPR tools to make them more accurate. With any given gRNA, these enhanced tools are less likely to edit the wrong DNA sequences.

Finally, turning off CRISPR tools can decrease the chances for off-target effects. To understand why, think of CRISPR tools like super accurate archers. With enough shots, even the most accurate archer will miss their target at some point. Similarly, CRISPR tools will edit the wrong DNA sequences if given enough time. Thus, off-switches limit the amount of time CRISPR tools are functional, giving them fewer chances to make mistakes.

Scientists use anti-CRISPRs - proteins that block CRISPR tools - to turn CRISPR "off."

Unintended effects of genome editing

Safer CRISPR tools will result in more therapeutic impacts

While defending us, the immune system searches for non-human proteins or parts of them. Normally such proteins come from infectious microbes. If immune cells find these proteins, they sound alarms and activate immune responses.

CRISPR proteins come from bacteria and archaea and can activate immune responses in human patients. These immune responses might stop CRISPR therapies before they can help patients. Strong immune responses can also cause acute inflammation, which can make patients sicker.

Researchers overcome immune responses in a few ways. First, they can give patients immunosuppressive drugs. These lower immune responses and mitigate adverse reactions. Such drugs are widely used in clinical settings and are particularly important for things like organ transplants. They are very useful but, as a side effect, increase the potential for infections.

Researchers also hope to lower the potential for immune responses by altering the make-up of their CRISPR proteins. These altered proteins wouldn't recognized by the immune system, so they're less likely to rouse immune responses.

Finally, researchers can turn on and off the production of CRISPR proteins. With these capabilities, researchers can produce CRISPR proteins only when and where they are needed. As a result, there will be fewer CRISPR proteins in the body. With less protein, immune responses are less likely and less severe when they do occur.

ILLUSTRATION USE & ATTRIBUTION

We encourage you to use and adapt CRISPRpedia illustrations for non-commercial, educational purposes. Tweet us @igisci to show us how you're using them! ALL uses and modifications must follow the Creative Commons BY-NC-SA 4.0 International License.

Over time, researchers will get better at reducing the risks of CRISPR-based treatments. It is safe to assume that CRISPR therapies will have greater positive impacts on health over time, too.

# data[].attributes.attachment_link.description
CRIPSR in Medicine: Learn how doctors and researchers can use CRISPR tools to improve human health by treating and preventing diseases.

# data[].attributes.body
Innovative Genomics Institute

# data[].attributes.attachment_link.readable_text
2022 marked the 10th anniversary of the development of CRISPR as a genome-editing tool - and the first year that CRISPR-edited foods could be found on a grocery store shelf. In this article, we'll go over the basics of genomic engineering in agriculture and then map out some of the most exciting new developments in 2022 from applications in crops and livestock. These include changing traits to adapt to a changing climate, improving taste or nutrition, protecting staple crops from disease, and more! We'll also touch on the shifting regulatory landscape and what to watch for next.

ADDING CRISPR TO THE TOOLKIT

Relationships between humans, plants, and animals fundamentally changed with the introduction of agriculture, from exclusively making use of what was available in wild settings to intentional cultivation in novel settings. Farmers began selecting for crops and livestock with desirable traits like corn with many kernels or fruits with fewer toxins. They carried forward the organisms with these traits from generation to generation, in a process known as selective breeding.

Selective breeding was the first of many subsequent human interventions into agriculture, eventually complemented by newer techniques. For example, in crop plants techniques like , breeding, and now cross-pollination mutation breeding, transgenic gene editing are all in a lineage of tools with the goal of improving agriculture. Each of these approaches alters the genome - but CRISPR does it with unprecedented precision. From selective breeding to CRISPR we ask: How can we leverage these tools to generate crops and livestock that meet our needs?

In the news, you might hear about how CRISPR is already advancing human health: researchers are using CRISPR to delve deeper into the genetic basis of disease and CRISPR-based therapies are showing impressive results in clinical trials. Over the last decade, CRISPR has also been used to make genetic changes in a sweeping range of organisms beyond humans - including some of our most important and beloved crops and livestock.

CRISPR tools work similarly whether in a human, animal, or plant cell: they cut DNA at a specific site, programmed in by a researcher. This cut in the DNA signals the cell to recruit repair machinery. In the process of repairing the broken DNA, changes are sometimes made to the DNA. We can harness this process to develop new understandings of biological organisms, new cures for diseases, and new agricultural innovations. So far in agriculture, CRISPR is usually used to generate genetic "knockouts": changes to genes that make them stop working.

The big difference between animals and plants is how the gene-editing machinery is delivered into cells. In plants, two primary methods are used. In one, the bacterium Agrobacterium tumefaciens is used to transfer genes into plant genomes. In the other, gold-plated DNA is projected at plant tissues at high speeds and pressures to penetrate into the plant cell. Afterwards, the cells are grown into whole plants ready for research.

In fish, injecting gene-editing machinery directly into eggs is usually the most efficient way to produce gene-edited organisms. In mammals used in research and agriculture, two methods are used to generate edited embryos prior to transfer to a surrogate. In one, fertilized eggs are directly edited. The other uses somatic cell nuclear transfer, conventionally known as cloning. In this process, all the DNA in a fertilized egg is taken out and the DNA from an edited cell line is transferred in to make an gene-edited embryo. Note that these techniques are not currently being used in .

FROM LAB TO PLATE

In the United States, most gene-edited crops have genetic changes that could occur in nature and are exempted from regulation. Producers can request a confirmation from the USDA to ensure that the plant they developed meets the criteria for the exemption. Once a plant is given exempt status, it can be marketed, scaled, and distributed to growers and consumers alike. Depending on the specific changes, the FDA or EPA may also be involved in regulation. In the case of gene-edited animals, the FDA must approve the animal for commercialization.

Once an animal or plant is reviewed by regulatory agencies and deemed safe, it can be marketed, scaled, and distributed to growers and consumers alike.

In this article, we break down the advances in CRISPR for agriculture into three major categories based on who primarily benefits - consumers, farmers, or the planet - with examples of interesting and notable products that are in the development pipeline. For each example, we denote where in the lab-to-field pipeline a gene-edited agricultural organism is.

GRAPHIC SUMMARY
Where are genome-edited products in the development pipeline? Hover over the icons to explore!
A graphical overview of the examples discussed in this article and their progress from research to commercial availability. Let your cursor hover over the icons for more info on each product. The microscope icon indicates products in the lab research stage; the wheat icon indicates products undergoing field trials; and the fork and knife indicate products that are commercialized. You'll also see a checkmark symbol used in this article, indicating products given the green-light for commercialization.

EDITING FOR THE EATER: CONSUMER BENEFITS

Consumers - in this case, anyone who eats - have broad preferences and desires. Gene editing is a potent mechanism to deliver on these far-ranging food interests. Over the past year, researchers have used CRISPR to deliver nutritious leafy greens with milder flavor, long-lasting bananas, and tomatoes with higher GABA content. For the first time ever, food generated using CRISPR technology is being sold to consumers.

Japanese food markets are world-renowned for the incredible quality of fish and huge array of rice varieties, among many other gleaming foodstuffs. They now have a new distinction: people in Japan are the first consumers in the world with access to gene-edited produce.

One of these options is the GABA tomato. Permitted by Japanese authorities in 2021, this tomato has found its way to thousands of home gardeners, farmers, and consumers in 2022. Produced by Tokyo-based Sanatech Seeds, these have been edited to increase the accumulation of γ-aminobutyric acid or GABA. This compound is widely consumed as a supplement with claims of lowering blood pressure, improving mood, and increasing relaxation. While the clinical evidence supporting these claims is less than substantial, there is tremendous interest in GABA-enriched products in Japan. CRISPR-based editing of a single tomato gene produced lines with 4-20 times greater GABA levels. The verdict is still out whether GABA-rich tomatoes can provide real health benefits, but either way, being the first gene-edited product to hit supermarket shelves is a distinction!

In the quest to assemble a gene-edited salad, one might add a GABA tomato to their cart alongside Conscious Greens. Recently unveiled by Pairwise, these have been gene edited to reduce the pungency of notoriously bitter mustard greens.

Using CRISPR, researchers at Pairwise transformed the nutritious but boldly-flavored leafy green into a milder salad green with the same nutritional profile. By editing a family of genes that catalyze the reaction known as the "mustard bomb," these leafy greens have been disarmed into a more palatable form. Biochemical and sensory evaluations of these greens have validated that the source of the pungent flavors remains stably suppressed in fields and greenhouses.

Conscious Greens have recently made their way into the mouths and hearts of the public in various American cities where tasting events were hosted by the company. In 2023, they will be available in American grocery stores and restaurants.

Few fruits are as ubiquitously loved and consumed as the banana. With a built-in wrapper and a sweet treat within, bananas have earned their spot as the most widely consumed fruit in the world.

Following the example of other non-browning products like the Arctic apple or the non-browning mushroom , Tropic Biosciences has achieved a similar type of product, this time using gene editing: a that can resist browning.

When exposed to oxygen, bananas and many other favorite foods like apples and avocados will start to brown. Thereactions that cause browning also usher in unpleasant flavors and odors, as well as reductions in nutritional quality. By removing the function of the enzyme that facilitates this reaction using CRISPR, bananas can stay yellow longer, appeasing consumers, and potentially reducing food waste. The USDA has given the banana the go-ahead for commercialization.

Vitamin D is crucial for bone health and regulating the immune system, and deficiency increases the risk of a range of health problems, including certain cancers, metabolic disorders, and worsened COVID-19 severity. Nearly 1 billion people have insufficient vitamin D levels. Food is the primary source of vitamin D and dietary interventions may be our best bet for addressing vitamin D deficiency.

Using CRISPR, scientists successfully removed the function of a gene responsible for converting 7-DHC, a vitamin D precursor, into the next compound in the biochemical process that eventually leads a plant to make vitamin D. Tomatoes with edits accumulated high levels of vitamin D precursor in leaves and fruit. These plants could then be exposed to UV light, in a process that mirrors sun exposure, to yield tomatoes with high levels of vitamin D. A single edited tomato can provide nearly 20% of the recommended daily allowance of vitamin D, with opportunities for greater accumulation possible still.

With nearly one-third of the global population affected by some type of micronutrient deficiency, this represents one of the most exciting uses of CRISPR in agriculture. Gene editing has the potential to provide solutions for a range of deficiencies beyond Vitamin D.

EDITING FOR A BOUNTIFUL HARVEST: HIGH YIELD

Whether it's the Mid-Autumn festival or Sukkot, Mehregan, or the Andean Harvest Fiestas, nearly every culture in every corner of the Earth finds a way to honor the gifts of the harvest and to ask for abundant returns. Anxiety and celebration of crop and livestock yield is a thread woven through human experience that persists as threats to global food supply constantly emerge, alongside technological innovations like gene editing that could hold solutions.

In 2022, researchers worked on generating novel solutions to the evergreen issue of yield in agriculture. Some of these researchers made use of gene editing as a mechanism to achieve this end - with great success.

To pair with the GABA-rich tomato, a Kyoto-based start-up, in collaboration with Kyoto and Kindai Universities has developed two gene-edited fish , red sea bream and tiger puffer, now available for purchase in Japan. Both fish were CRISPR-edited to grow larger.

In tiger puffer, gene editing was used to interrupt the function of genes associated with appetite regulation, leading the fish to eat more, ultimately increasing its growth rate and overall size. The edited tiger puffer weighs nearly twice as much as its conventional counterpart and can be market-ready in a shorter period of time.

The red sea bream is edited in the myostatin gene, which typically limits muscle development. Edited red sea bream fed the same quantity of food grew 1.2x larger than conventional sea bream. This same gene has been experimentally edited in sheep, cattle, pig, goat, rabbit, carp, and catfish, among other animals. Though successful in sea bream, editing this gene in other livestock sometimes causes health problems.

While these edited fish products may seem like something out of sci-fi, shortening time to market and increasing the amount of edible flesh per animal decreases the carbon footprint of raising livestock and increases the abundance of food available. Now available in Japanese markets, the tiger puffer and red sea bream alongside the GABA tomato comprise the three first commercially available gene-edited foods.

Just a handful of crops occupy a grossly outsized proportion of our global calories. Despite hundreds of edible plant species, crops like maize, wheat, and rice comprise the majority of total crops consumed. Before they occupied such a gargantuan portion of our diets, these organisms didn't look much different than the weedy grasses gardeners and farmers remove from their plots. The process by which these wild crop ancestors were transformed into the varieties planted globally is known as domestication. Selection for traits like larger and more numerous grains marked the genetic and aesthetic transition of these plants into the universally consumed and beloved foods that fuel us.

Researchers are able to study the genetic shifts that occurred in domestication by comparing the genomes of wild crop ancestors to those of modern varieties. By increasing our genetic understanding of this process, they are able to select gene targets for CRISPR-editing that could result in even greater yields.

One of these targets, KRN2, a gene involved in determining the size of the group of cells that will give rise to flowers and ultimately grains, was edited in rice and maize . This led to increasing yields by 8% and 10%, respectively. These increases represent major leaps forward especially when compared to near-stagnant yield improvements in conventional breeding programs. What's more, the approach of looking to wild crop ancestors for a high-yielding path forward could be promising for other crop species as well.

CRISPR-Combo for Newer, Faster Edits

An advancement in plant genome engineering was achieved this year by researchers at the University of Maryland. Scientists produced a new tool named that works to simultaneously knockout target genes while activating others. Alternatively, CRISPR-Combo can be used to make precise changes to DNA using CRISPR-Combo base editing - a kind of CRISPR-editing that can make tweaks to individual genetic letters without the need to break the DNA - while simultaneously activating other genes.

A major bottleneck in plant gene editing is the lengthy process of forming a whole plant from an initial edited cell. CRISPR-Combo can be used to activate genes that help plants regenerate faster, as demonstrated in poplar, rice, and , a plant commonly used in lab research. Excitingly, this tool can also increase the ease and speed of selecting plants that are Arabidopsis thaliana transgene free, meaning that only the edits remain and no foreign DNA. This can help produce plants that can more easily pass through regulation.

The process of domestication was used on many crops to produce the modern varieties we grow today. Sometimes, the suite of traits typically associated with domestication - like larger fruits, more uniform time to maturity, and loss of toxic compounds - is only partially present in a given plant. These plants are known as semi-domesticated and have great potential for further improvement. This is the case for teff, a grain crop grown primarily in Ethiopia and Eritrea.

Teff is the most widely cultivated grain crop in Ethiopia. It is resistant to pests and diseases, and can grow in a wide range of environmental extremes unsuitable for other grass crops. However, this important grain crop still suffers from many disadvantages associated with undomesticated grasses. One of the primary limitations of higher-yielding teff production is its susceptibility to "lodging," a process in which stems buckle under the weight of heavy grains near the top of the plant.

EDITING FOR A DYNAMIC PLANET:
CLIMATE & DISEASE RESISTANCE

Climate change is bringing more erratic rainfall, increased drought severity, warmer temperatures, and saltier soils, and these effects will intensify over the next decades. The scientific consensus: agricultural productivity will decline.

While the rate of climate change is unprecedented, what is not new is the ability of agricultural technology to respond to pressing demands. New varieties of crops are released consistently for traits that meet the moment, whether that be resistance to a papaya virus or a more nutritious sweet potato .

In a similar way, gene editing may offer another tool to address the severe effects climate change is already starting to have on agriculture.

Beyond the novelty of being permitted, what is so special about these cattle, anyways? Warming temperatures cause physiological stress to cattle: their body temperature increases, their breathing speeds up, and in dairy cows, milk production goes down. The cattle in this example have an edit that gives them short-hair, also known as a "slick" coat. Shorter hair means that these Travolta-esque slick cows can stay cooler in warm temperatures, increasing animal welfare and ultimately beef production in a changing climate.

The changes made by gene editing resemble naturally occurring variations in the same gene often found in tropical cattle breeds. Gene editing enables the transfer of this short-haired trait into good meat-producing breeds in a streamlined manner. In other words, CRISPR is giving overheated cows a genetic haircut and the ability to yield well despite a warming world.

Removing the function of genes by gene editing can sometimes deliver desirable results like high-yielding wheat or tastier greens. However, sometimes the genes that control traits of interest have more than one job. This is especially true for genes known as "susceptibility genes". Disrupting the function of disease susceptibility genes can give crops resistance to diseases but often also results in lower yield.

As the climate changes, it is expected that infectious diseases will get more severe. Changes to the climate can create environments that are more favorable for pathogens and for the vectors, like insects, that help spread those pathogens. This study shows that when strategically applied, gene editing may help plants and animals resist diseases - without yield losses.

Senecavirus A (SVA) is an increasingly damaging disease in the swine industry. Increasing understanding of how this virus works in could help researchers develop strategies for managing its spread.

In a recent study, CRISPR was used to remove the function of a pig gene named ANTXR1. This gene was thought to be a receptor for SVA in pigs. Indeed, disrupting the ANTXR1 gene using CRISPR resulted in pigs that had dramatically lower levels of virus. Unfortunately, pigs with this edit had other undesired attributes, such as cataracts at birth.

In this case, simply removing the function of this gene is not a viable option for preventing infection. The improved understanding of viral infection facilitated via CRISPR may enable the development of new strategies for virus mitigation in swine.

THE BIG PICTURE

This year, for the first time ever, multiple gene-edited foods were available to the public! Landing on the shelves of Japanese shoppers were gene-edited red sea bream, puffer fish, and GABA-rich tomatoes. New varieties and breeds permitted by the USDA and FDA, like the milder mustard greens and the heat-tolerant cow, will likely be available to consumers in the coming months or years.

We can expect more products to arrive in grocery stores as different countries around the globe outline clear paths to commercialization. India, Kenya, and the joined a growing list of countries to develop regulation regarding gene-edited crops this year. Without clear regulation, gene-edited products cannot be legally commercialized. These new policies are a significant step towards expanding the global presence of gene-edited foodstuffs by offering a pipeline to commercialization. Over the last couple decades, the regulation of Philippines GMO products was largely determined by movements in Europe. In contrast, new regulations on gene-edited products from Asia and Africa signal a shift in power towards greater market autonomy.

Beyond new enabling policy, technological advances stand to accelerate the development of new gene-edited crops and livestock. Currently, gene editing is largely used to make gene "knockouts". The emergence of technology like CRISPR-Combo that can help researchers more effectively make other kinds of genetic changes like turning a gene "up" or adding new DNA sequences, gets us closer to ultimately leveraging the full, versatile capacity of CRISPR.

WHAT TO WATCH FOR

Looking forward, we can expect that CRISPR-edited crops and livestock will continue to emerge in the literature, the lab, and even in our markets over the next couple years, aimed at traits related to climate adaptation, consumer quality improvement, and yield enhancement. Keep an eye out for gene edits that go beyond the simple "knockout" in favor of precise gene insertions, base edits, or multiple types of edits simultaneously: these will represent growing use of more technically complex edits. The European Union , which has some of the most restrictive regulation of gene-edited products, has indicated that they're working on a fast-track approval process for crops that are edited for sustainability. We also expect updates to US policies and that nations in South America, Asia, and Africa will continue to develop new gene-editing regulations.

The technological power of CRISPR is uncontested. But the ultimate impact remains to be seen: impact depends on implementation, which includes favorable regulation, grower education, public understanding and acceptance. It is not just technological innovation, but navigating the complex sociopolitical landscape of food systems, that is crucial to how - and how much - gene editing takes root as a mainstay of our food system.

By Nicholas Karavolias

# data[].attributes.attachment_link.description
The use of CRISPR in agriculture is becoming more common around the world. A review of the progress in 2022 and what is coming next.

# data[].attributes.attachment_caption
Creative Commons Copyright (c) 2022 Lightspring/Shutterstock

# data[].attributes.body
Genetically Modified Food

# data[].attributes.body
"CRISPR-Cas9 is a customizable tool that lets scientists cut and insert small pieces of DNA at precise areas along a DNA strand. This lets scientists study our genes in a specific, targeted way."

Credit: Ernesto del Aguila III, National Human Genome Research Institute, NIH

# data[].attributes.headline
Genetic Engineering Will Change Everything Forever – CRISPR

# data[].attributes.subject
Genetic Engineering Will Change Everything Forever – CRISPR

# data[].attributes.body
Video Created By: Kurzgesagt

# data[].attributes.attachment_link.title
Genetic Engineering Will Change Everything Forever – CRISPR

# data[].attributes.body
Vigliotti, Vivian S., and Isabel Martinez. “Public health applications of CRISPR: How children’s health can benefit.” Seminars in Perinatology, vol. 42, no. 8, Dec. 2018, pp. 531–536, https://doi.org/10.1053/j.semperi.2018.09.017.

# data[].attributes.attachment_link.title
Public health applications of CRISPR: how children’s health can benefit

# data[].attributes.attachment_link.description
Children under the age of five years old face significant mortality risks around the world. Public health innovations, particularly gene-editing technologies such as clustered regularly interspaced short palindromic repeats (CRISPR) could help to reduce…