# data[].attributes.body
There are two types of gene therapy, Germaine and somatic. Germaine is injecting a new cc cell through the egg and sperm. Somatic is changing the cell through the body tissue.

# data[].attributes.attachment_link.readable_text
Gene therapy is when DNA is introduced into a patient to treat a genetic disease. The new DNA usually contains a functioning gene to correct the effects of a disease-causing mutation.

Gene therapy uses sections of DNA (usually genes) to treat or prevent disease.

The DNA is carefully selected to correct the effect of a mutated gene that is causing disease.

The technique was first developed in 1972 but has, so far, had limited success in treating human diseases.

Gene therapy may be a promising treatment option for some genetic diseases, including muscular dystrophy and cystic fibrosis.

There are two different types of gene therapy depending on which types of cells are treated:

Somatic gene therapy: transfer of a section of DNA to any cell of the body that doesn't produce sperm or eggs. Effects of gene therapy will not be passed onto the patient's children.

Germline gene therapy: transfer of a section of DNA to cells that produce eggs or sperm. Effects of gene therapy will be passed onto the patient's children and subsequent generations.

Gene therapy techniques

There are several techniques for carrying out gene therapy. These include:
Gene augmentation therapy

This is used to treat diseases caused by a mutation that stops a gene from producing a functioning product, such as a protein.

This therapy adds DNA containing a functional version of the lost gene back into the cell.

The new gene produces a functioning product at sufficient levels to replace the protein that was originally missing.

This is only successful if the effects of the disease are reversible or have not resulted in lasting damage to the body.

For example, this can be used to treat loss of function disorders such as cystic fibrosis by introducing a functional copy of the gene to correct the disease (see illustration below).

Gene inhibition therapy

Suitable for the treatment of infectious diseases, cancer and inherited disease caused by inappropriate gene activity.

The aim is to introduce a gene whose product either:

inhibits the expression of another gene

interferes with the activity of the product of another gene.

The basis of this therapy is to eliminate the activity of a gene that encourages the growth of disease-related cells.

For example, cancer is sometimes the result of the over-activation of an oncogene (gene which stimulates cell growth). So, by eliminating the activity of that oncogene through gene inhibition therapy, it is possible to prevent further cell growth and stop the cancer in its tracks.

Killing of specific cells

Suitable for diseases such as cancer that can be treated by destroying certain groups of cells.

The aim is to insert DNA into a diseased cell that causes that cell to die.

This can be achieved in one of two ways:

the inserted DNA contains a "suicide" gene that produces a highly toxic product which kills the diseased cell

the inserted DNA causes expression of a protein that marks the cells so that the diseased cells are attacked by the body's natural immune system.

It is essential with this method that the inserted DNA is targeted appropriately to avoid the death of cells that are functioning normally.

How is DNA transfer done?

A section of DNA/gene containing instructions for making a useful protein is packaged within a vector, usually a virus, bacterium or plasmid.

The vector acts as a vehicle to carry the new DNA into the cells of a patient with a genetic disease.

Once inside the cells of the patient, the DNA/gene is expressed by the cell's normal machinery leading to production of the therapeutic protein and treatment of the patient's disease.

Challenges of gene therapy

Delivering the gene to the right place and switching it on:

it is crucial that the new gene reaches the right cell

delivering a gene into the wrong cell would be inefficient and could also cause health problems for the patient

even once the right cell has been targeted the gene has to be turned on

cells sometimes obstruct this process by shutting down genes that are showing unusual activity.

Avoiding the immune response:

The role of the immune system is to fight off intruders.

Sometimes new genes introduced by gene therapy are considered potentially-harmful intruders.

This can spark an immune response in the patient, that could be harmful to them.

Scientists therefore have the challenge of finding a way to deliver genes without the immune system 'noticing'.

This is usually by using vectors that are less likely to trigger an immune response.

Making sure the new gene doesn't disrupt the function of other genes:

Ideally, a new gene introduced by gene therapy will integrate itself into the genome of the patient and continue working for the rest of their lives.

There is a risk that the new gene will insert itself into the path of another gene, disrupting its activity.

This could have damaging effects, for example, if it interferes with an important gene involved in regulating cell division, it could result in cancer.

The cost of gene therapy:

Many genetic disorders that can be targeted with gene therapy are extremely rare.

Gene therapy therefore often requires an individual, case-by-case approach. This may be effective, but may also be very expensive.

# data[].attributes.attachment_link.description
Gene therapy is when DNA is introduced into a patient to treat a genetic disease. The new DNA usually contains a functioning gene to correct the effects of a disease-causing mutation. Gene therapy uses sections of DNA (usually genes) to treat or prevent disease.

# data[].attributes.body
The evolution of gene therapy and the people who thought of it. A timeline of when certain ideas were made and what doctor made it happen

# data[].attributes.attachment_link.readable_text
Cord blood has been studied extensively for the treatment of hematological diseases such as cancer and sickle cell anemia, but is now in phase II trials for the alleviation of autism. Dr. Ann Smith, director of Smart Cells who provided the cord blood for the trial, discusses the research and it's potential.

# data[].attributes.attachment_link.description
Cord blood has been studied extensively for the treatment of hematological diseases such as cancer and sickle cell anemia, but is now in phase II trials for the alleviation of autism. Dr. Ann Smith, director of Smart Cells who provided the cord blood for the trial, discusses the research and it's potential.

# data[].attributes.body
Telling you the definition, why its done, the risks and all you need to know about the gene therapy.
K.C.

# data[].attributes.attachment_link.description
Learn about gene therapy, which replaces a faulty gene or adds a new gene in an attempt to cure disease or improve your body's ability to fight disease.

# data[].attributes.body
This talks about what gene therapy is and how it works. It also says that the genes go back to normal but there can also be problems in the change.
K.C.

# data[].attributes.body
This tells us about how the genes are design in the laboratory. Making RNA and DNA.
KC.

# data[].attributes.attachment_link.readable_text
Studying the effects of gravity on muscle cells can give us an insight into muscle wastage diseases, and potentially guide the development of new therapies. Professor Louis Yuge discusses his research and the cellular changes that occur in response to microgravity.

# data[].attributes.attachment_link.description
Studying the effects of gravity on muscle cells can give us an insight into muscle wastage diseases, and potentially guide the development of new therapies. Professor Louis Yuge discusses his research and the cellular changes that occur in response to microgravity.

# data[].attributes.body
DM

Before beginning the procedure, it is important for the researchers to have the patients' consent and inform them about the risks and benefits. If the procedure keeps failing in many trials, then the researcher should change the study or not make any more trials.The product must also obtain a permission exemption from the U.S. Food and Drug Administration. The FDA's must also protect the health of U.S. citizens by ensuring that the medicine and biological products are safe to use.

# data[].attributes.attachment_link.readable_text
In the United States, the Department of Health and Human Services (DHHS) has been charged with oversight of clinical trials. Two organizations within DHHS, the Office for Human Research Protections (OHRP) and the U.S. Food and Drug Administration (FDA), have specific authority described in the Code of Federal Regulations (CFR). All investigators, must comply with these regulations when conducting clinical gene therapy trials. The OHRP mandates that all research involving human subjects undergo Institutional Review Boards (IRB) review and approval. An IRB is charged with evaluating research risk to subjects and must approve research protocols and informed consent documents prior to beginning a study.
Another DHHS agency, the National Institutes of Health (NIH), oversees the conduct of federally funded clinical trials through a series of guidelines that add additional requirements to those specified in the CFR.

NIH - OBA - RAC
The NIH established the Recombinant DNA Advisory Committee (RAC) on October 7, 1974 in response to public concerns regarding the safety of manipulating genetic material through the use of recombinant DNA techniques. Although the RAC's responsibilities have evolved over time with scientific understanding and developments in this technology, it continues to serve the NIH as a critically important forum for open, public deliberation on the panoply of scientific, ethical, and legal issues raised by recombinant DNA technology and its basic and clinical research applications. A major responsibility of the RAC at present is to review human gene transfer research on behalf of the NIH. Human gene transfer trials conducted at, or sponsored by, institutions receiving NIH funding for recombinant DNA research are registered with the Office of Biotechnology Activities (OBA) and reviewed by the RAC. The OBA is responsible for the NIH system of oversight of recombinant DNA research. Clinical gene therapy protocols that raise novel or particularly important scientific, safety or ethical considerations are discussed by the RAC at one of its quarterly public meetings. RAC proceedings and reports are posted to the OBA website to enhance their accessibility to the scientific and lay publics.
The NIH also consults the RAC for advice concerning various advances in recombinant DNA technology, as well as ethical and safety considerations associated with novel or possibly risky forms of recombinant DNA research.

FDA - CBER
The U.S. Food and Drug Administration (FDA) is the primary government agency charged with protecting the health of U.S. citizens by ensuring that drugs, medical devices and biological products are safe and effective before they are used by doctors, nurses, other health care professionals, hospitals and consumers.
FDA's Center for Biologics Evaluation and Research (CBER) regulates human gene therapies, which fall under the legal definition of a "biologic." Manufacturers of gene therapy products must test their products extensively and meet FDA requirements for safety, purity and potency before they can be sold in the United States. A manufacturer who is considering selling a gene therapy product in the United States first must tell FDA of its intentions, and then must test the product in a laboratory and then in research animals. When a manufacturer is ready to study the gene therapy product in humans, it must obtain a special permission exemption from FDA before starting. This exemption is called an investigational new drug application or (IND). In the IND, the manufacturer explains how it intends to conduct the study, what possible risks may be involved and what steps it will take to protect patients, and provides data in support of the study. As part of the IND process, the manufacturer also must get approval from a committee of scientific and medical advisors and consumers (called an Institutional Review Board), which focuses on protecting persons who may participate in the study. Researchers also must inform the persons who may be part of the study about the study's potential risks and benefits, and obtain their consent.
When FDA's scientists receive an IND application for gene therapy, they review it carefully before permitting the manufacturer or researcher to begin the study. FDA may ask the study sponsor to do more laboratory tests and include more safeguards to ensure the safety of patients, such as giving patients smaller doses. As discussed in the next section, if unexpected problems arise, FDA may tell the manufacturer to change the study or stop it altogether.
FDA has not yet approved for sale any human gene therapy product.

# data[].attributes.attachment_link.description
In the United States, the Department of Health and Human Services (DHHS) has been charged with oversight of clinical trials. Two organizations within DHHS, the Office for Human Research Protections (OHRP) and the U.S. Food and Drug Administration (FDA), have specific authority described in the Co...

# data[].attributes.headline
How Does Gene Therapy Work?                DM                                                                         

# data[].attributes.subject
How Does Gene Therapy Work?                DM                                                                         

# data[].attributes.body
In order to place a gene into  a human cell, a vector must be used as a carrier to deliver the gene. A vector can be used as certain viruses because they can infect the cell to deliver the gene. This process can begin with an injection through the cell membrane and travel into a cell.

# data[].attributes.attachment_link.description
The vector can be injected or given intravenously (by IV) directly into a specific tissue in the body, where it is taken up by individual cells. Alternately, a sample of the patient's cells can be removed and exposed to the vector in a laboratory setting.

# data[].attributes.body
Gene therapy can help but not completely cure some diseases.
D.F

# data[].attributes.attachment_link.readable_text
This week, scientists will gather in Washington, D.C., for an annual meeting devoted to gene therapy-a long-struggling field that has clawed its way back to respectability with a string of promising results in small clinical trials. Now, many believe the powerful new gene-editing technology known as CRISPR will add to gene therapy's newfound momentum. But is CRISPR really ready for prime time? Science explores the promise-and peril-of the new technology.

How does CRISPR work?

Traditional gene therapy works via a relatively brute-force method of gene transfer. A harmless virus, or some other form of so-called vector, ferries a good copy of a gene into cells that can compensate for a defective gene that is causing disease. But CRISPR can fix the flawed gene directly, by snipping out bad DNA and replacing it with the correct sequence. In principle, that should work much better than adding a new gene because it eliminates the risk that a foreign gene will land in the wrong place in a cell's genome and turn on a cancer gene. And a CRISPR-repaired gene will be under the control of that gene's natural promoter, so the cell won't make too much or too little of its protein product.

What has CRISPR accomplished so far?

Researchers have published successes with using CRISPR to treat animals with an inherited liver disease and muscular dystrophy, and there will be more such preclinical reports at this week's annual meeting of the American Society of Gene and Cell Therapy (ASGCT). The buzz around CRISPR is growing. This year's meeting includes 93 abstracts on CRISPR (of 768 total), compared with only 33 last year. What's more, investors are flocking to CRISPR. Three startups, Editas Medicine, Intellia Therapeutics, and CRISPR Therapeutics, have already attracted hundreds of millions of dollars.

So why isn't CRISPR ready for prime time?

CRISPR still has a long way to go before it can be used safely and effectively to repair-not just disrupt-genes in people. That is particularly true for most diseases, such as muscular dystrophy and cystic fibrosis, which require correcting genes in a living person because if the cells were first removed and repaired then put back, too few would survive. And the need to treat cells inside the body means gene editing faces many of the same delivery challenges as gene transfer-researchers must devise efficient ways to get a working CRISPR into specific tissues in a person, for example.

CRISPR also poses its own safety risks. Most often mentioned is that the Cas9 enzyme that CRISPR uses to cleave DNA at a specific location could also make cuts where it's not intended to, potentially causing cancer.

With these caveats, do you even need CRISPR?

Conventional gene addition treatments for some diseases are so far along that it may not make sense to start over with CRISPR. In Europe, where one gene therapy is already approved for use for a rare metabolic disorder, regulators are poised to approve a second for an immune disorder known as adenosine deaminase-severe combined immunodeficiency (SCID). And in the United States, a company this year expects to seek approval for a gene transfer treatment for a childhood blindness disease called Leber congenital amaurosis (LCA).

At the ASCGT meeting, researchers working with the company Bluebird Bio will present interim data for a late-stage trial showing that gene addition can halt the progression of cerebral adrenoleukodystrophy, a devastating childhood neurological disease. Final results could help pave the way for regulatory approval. Bluebird will also report on trials using gene transfer for two blood disorders, sickle cell disease and β-thalassemia, bringing these treatments closer to the clinic.

Except for LCA, in which gene-carrying viruses are injected directly into eyes, these diseases are treated by removing bone marrow cells from patients, adding a gene to the cells, and reinfusing the cells back into the patient. New, safer viral vectors have reduced risks of leukemia seen in a few patients in some early trials for immunodeficiency diseases. Researchers are seeing "excellent clinical responses," says Donald Kohn of the University of California, Los Angeles.

Although Kohn and other researchers have used an older gene-editing tool known as zinc finger nucleases to repair defective genes causing sickle cell disease and a type of SCID in cells in a dish, only a tiny fraction of immature blood cells needed for the therapy to work end up with the gene corrected-far below the fraction altered by now standard gene transfer methods. One reason is because the primitive blood cells aren't dividing much (more on this below). Because gene-editing methods such as CRISPR are so much less efficient than gene addition, for several diseases, "I don't think there will be a strong rationale for switching to editing," says Luigi Naldini of the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy.

CRISPR also has other issues

Using CRISPR to cut out part of a gene-not correct the sequence-is relatively easy to do. In fact, this strategy is already being tested with zinc finger nucleases in a clinical effort to stop HIV infection. In this treatment, the nucleases are used to knock out a gene for a receptor called CCR5 in blood cells that HIV uses to get into cells.

But when CRISPR is used to correct a gene using a strand of DNA that scientists supply to cells, not just to snip out some DNA, it doesn't work very well. That's because the cells must edit the DNA using a process called homology-directed repair, or HDR, that is only active in dividing cells. And unfortunately, most cells in the body-liver, neuron, muscle, eye, blood stem cells-are not normally dividing. For this reason, "knocking out a gene is a lot simpler than knocking in a gene and correcting a mutation," says Cynthia Dunbar, president-elect of ASGCT and a gene therapy researcher at the National Heart, Lung, and Blood Institute in Bethesda, Maryland.

Researchers are working on ways to get around this limitation. The genes for HDR are present in all cells, and it's a matter of turning them on, perhaps by adding certain drugs to the cells, says CRISPR researcher Feng Zhang of the Broad Institute in Cambridge, Massachusetts. Another avenue is to find alternatives to the Cas9 system that don't rely on the HDR process, Zhang says.

But the low rate of HDR in most cells is one reason why the first use of CRISPR in the clinic will likely involve disrupting genes, not fixing them. For example, several labs have shown in mice that CRISPR can remove a portion of the defective gene that causes Duchenne muscular dystrophy, so that the remaining portion will produce a functional, albeit truncated protein. Editas hopes to start a clinical trial next year to treat a form of LCA blindness by chopping out part of the defective gene. One proposed gene-editing treatment for sickle cell disease would similarly snip out some DNA, so that blood cells produce a fetal form of the oxygen-carrying protein hemoglobin.

And CRISPR still has big safety risks

The most-discussed safety risk with CRISPR is that the Cas9 enzyme, which is supposed to slice a specific DNA sequence, will also make cuts in other parts of the genome that could result in mutations that raise cancer risk. Researchers are moving quickly to make CRISPR more specific. For example, in January, one lab described a tweak to Cas9 that dramatically reduces off-target effects. And in April in Nature, another team showed how to make the enzyme more efficient at swapping out single DNA bases.

But immediate off-target cuts aren't the only worry. Although it's possible to deliver CRISPR's components into cells in a dish as proteins or RNA, so far researchers can usually only get it working in tissue inside the body by using a viral vector to deliver the DNA for Cas9 into cells. This means that even after Cas9 has made the desired cuts, cells will keep cranking it out. "The enzyme will still hang around over 10, 20 years," Zhang says. That raises the chances that even a very specific Cas9 will still make off-target cuts and that the body will mount an immune response to the enzyme.

This may not truly be a problem, Zhang suggests. His team created a mouse strain that is born with the gene for Cas9 turned on all the time, so it expresses the enzyme in all cells for the animal's entire life. Even after interbreeding these mice for about 20 generations, the mice "seem to be fine" with no obvious abnormal health effects, Zhang says. All the same, "the most ideal case is, we want to shut off the enzyme." And that may mean finding nonviral methods for getting Cas9 into cells, such as ferrying the protein with lipids or nanoparticles-delivery methods that biologists have long struggled to make work in living animals.

Other long-standing obstacles to gene therapy will confront efforts using CRISPR, too. Depending on the disease, any gene-edited cells may eventually die and patients could have to be treated multiple times. Researchers using gene transfer and editing approaches are also both hindered by limits on how much DNA a viral vector can carry. Right now CRISPR researchers often must use two different viruses to get CRISPR's components into cells, which is less efficient than a single vector.

So what's the bottom line?

Gene therapists remain excited by CRISPR, in part because it could tackle many more inherited diseases than can be treated with gene transfer. Among them are certain immune diseases where the amount of the repaired protein must be precisely controlled. In other cases, such as sickle cell disease, patients won't get completely well unless a defective protein is no longer made by their cells, so just adding a gene isn't enough. "It opens up a lot of diseases to gene therapy because gene addition wasn't going to work," Dunbar says.

After more than 2 decades of seeing their field through ups and downs, veterans of the gene therapy field are wary of raising expectations about CRISPR for treating diseases. "Whenever there's a new technology, there's a huge amount of excitement and everybody thinks it will be ready tomorrow to cure patients," says gene therapy researcher Mark Kay of Stanford University in Palo Alto, California. "It's going to take some time."

# data[].attributes.attachment_link.title
The gene editor CRISPR won't fully fix sick people anytime soon. Here's why

# data[].attributes.attachment_link.description
This week, scientists will gather in Washington, D.C., for an annual meeting devoted to gene therapy-a long-struggling field that has clawed its way back to respectability with a string of promising results in small clinical trials. Now, many believe the powerful new gene-editing technology known as CRISPR will add to gene therapy's newfound momentum.

# data[].attributes.body
DM

The first step would be to have a vector genetically engineered to send off a gene. This can be injected or directly be sent off to a specific tissue in the body. However, some viruses are used as vectors

# data[].attributes.attachment_link.description
The vector can be injected or given intravenously (by IV) directly into a specific tissue in the body, where it is taken up by individual cells. Alternately, a sample of the patient's cells can be removed and exposed to the vector in a laboratory setting.

# data[].attributes.body
This shows the different kinds of gene therapy and how each one works.
K.C.

# data[].attributes.attachment_link.readable_text
Gene therapy is when DNA is introduced into a patient to treat a genetic disease. The new DNA usually contains a functioning gene to correct the effects of a disease-causing mutation.

Gene therapy uses sections of DNA (usually genes) to treat or prevent disease.

The DNA is carefully selected to correct the effect of a mutated gene that is causing disease.

The technique was first developed in 1972 but has, so far, had limited success in treating human diseases.

Gene therapy may be a promising treatment option for some genetic diseases, including muscular dystrophy and cystic fibrosis.

There are two different types of gene therapy depending on which types of cells are treated:

Somatic gene therapy: transfer of a section of DNA to any cell of the body that doesn't produce sperm or eggs. Effects of gene therapy will not be passed onto the patient's children.

Germline gene therapy: transfer of a section of DNA to cells that produce eggs or sperm. Effects of gene therapy will be passed onto the patient's children and subsequent generations.

Gene therapy techniques

There are several techniques for carrying out gene therapy. These include:
Gene augmentation therapy

This is used to treat diseases caused by a mutation that stops a gene from producing a functioning product, such as a protein.

This therapy adds DNA containing a functional version of the lost gene back into the cell.

The new gene produces a functioning product at sufficient levels to replace the protein that was originally missing.

This is only successful if the effects of the disease are reversible or have not resulted in lasting damage to the body.

For example, this can be used to treat loss of function disorders such as cystic fibrosis by introducing a functional copy of the gene to correct the disease (see illustration below).

Gene inhibition therapy

Suitable for the treatment of infectious diseases, cancer and inherited disease caused by inappropriate gene activity.

The aim is to introduce a gene whose product either:

inhibits the expression of another gene

interferes with the activity of the product of another gene.

The basis of this therapy is to eliminate the activity of a gene that encourages the growth of disease-related cells.

For example, cancer is sometimes the result of the over-activation of an oncogene (gene which stimulates cell growth). So, by eliminating the activity of that oncogene through gene inhibition therapy, it is possible to prevent further cell growth and stop the cancer in its tracks.

Killing of specific cells

Suitable for diseases such as cancer that can be treated by destroying certain groups of cells.

The aim is to insert DNA into a diseased cell that causes that cell to die.

This can be achieved in one of two ways:

the inserted DNA contains a "suicide" gene that produces a highly toxic product which kills the diseased cell

the inserted DNA causes expression of a protein that marks the cells so that the diseased cells are attacked by the body's natural immune system.

It is essential with this method that the inserted DNA is targeted appropriately to avoid the death of cells that are functioning normally.

How is DNA transfer done?

A section of DNA/gene containing instructions for making a useful protein is packaged within a vector, usually a virus, bacterium or plasmid.

The vector acts as a vehicle to carry the new DNA into the cells of a patient with a genetic disease.

Once inside the cells of the patient, the DNA/gene is expressed by the cell's normal machinery leading to production of the therapeutic protein and treatment of the patient's disease.

Challenges of gene therapy

Delivering the gene to the right place and switching it on:

it is crucial that the new gene reaches the right cell

delivering a gene into the wrong cell would be inefficient and could also cause health problems for the patient

even once the right cell has been targeted the gene has to be turned on

cells sometimes obstruct this process by shutting down genes that are showing unusual activity.

Avoiding the immune response:

The role of the immune system is to fight off intruders.

Sometimes new genes introduced by gene therapy are considered potentially-harmful intruders.

This can spark an immune response in the patient, that could be harmful to them.

Scientists therefore have the challenge of finding a way to deliver genes without the immune system 'noticing'.

This is usually by using vectors that are less likely to trigger an immune response.

Making sure the new gene doesn't disrupt the function of other genes:

Ideally, a new gene introduced by gene therapy will integrate itself into the genome of the patient and continue working for the rest of their lives.

There is a risk that the new gene will insert itself into the path of another gene, disrupting its activity.

This could have damaging effects, for example, if it interferes with an important gene involved in regulating cell division, it could result in cancer.

The cost of gene therapy:

Many genetic disorders that can be targeted with gene therapy are extremely rare.

Gene therapy therefore often requires an individual, case-by-case approach. This may be effective, but may also be very expensive.

# data[].attributes.attachment_link.description
Gene therapy is when DNA is introduced into a patient to treat a genetic disease. The new DNA usually contains a functioning gene to correct the effects of a disease-causing mutation. Gene therapy uses sections of DNA (usually genes) to treat or prevent disease.

# data[].attributes.body
This article shows what tests have been done and have been successful on people.
D.F

# data[].attributes.attachment_link.readable_text
Researchers have been working for decades to bring gene therapy to the clinic, yet very few patients have received any effective gene-therapy treatments. But that doesn't mean gene therapy is an impossible dream. Even though gene therapy has been slow to reach patients, its future is very encouraging. Decades of research have taught us a lot about designing safe and effective vectors, targeting different types of cells, and managing and minimizing immune responses in patients. We've also learned a lot about the disease genes themselves. Today, many clinical trials are underway, where researchers are carefully testing treatments to ensure that any gene therapy brought into the clinic is both safe and effective.

Below are some gene therapy success stories. Successes represent a variety of approaches-different vectors, different target cell populations, and both in vivo and ex vivo approaches-to treating a variety of disorders.

Sebastian Misztal was a patient in a hemophilia gene therapy trial in 2011. Following the treatment, Misztal no longer had spontaneous bleeding episodes.
Credit: UCLH/UCL NIHR Biomedical Research Centre

Several inherited immune deficiencies have been treated successfully with gene therapy. Most commonly, blood stem cells are removed from patients, and retroviruses are used to deliver working copies of the defective genes. After the genes have been delivered, the stem cells are returned to the patient. Because the cells are treated outside the patient's body, the virus will infect and transfer the gene to only the desired target cells.

Severe Combined Immune Deficiency (SCID) was one of the first genetic disorders to be treated successfully with gene therapy, proving that the approach could work. However, the first clinical trials ended when the viral vector triggered leukemia (a type of blood cancer) in some patients. Since then, researchers have begun trials with new, safer viral vectors that are much less likely to cause cancer.

Adenosine deaminase (ADA) deficiency is another inherited immune disorder that has been successfully treated with gene therapy. In multiple small trials, patients' blood stem cells were removed, treated with a retroviral vector to deliver a functional copy of the ADA gene, and then returned to the patients. For the majority of patients in these trials, immune function improved to the point that they no longer needed injections of ADA enzyme. Importantly, none of them developed leukemia.

Gene therapies are being developed to treat several different types of inherited blindness-especially degenerative forms, where patients gradually lose the light-sensing cells in their eyes. Encouraging results from animal models (especially mouse, rat, and dog) show that gene therapy has the potential to slow or even reverse vision loss.

The eye turns out to be a convenient compartment for gene therapy. The retina, on the inside of the eye, is both easy to access and partially protected from the immune system. And viruses can't move from the eye to other places in the body. Most gene-therapy vectors used in the eye are based on AAV (adeno-associated virus).

In one small trial of patients with a form of degenerative blindness called LCA (Leber congenital amaurosis), gene therapy greatly improved vision for at least a few years. However, the treatment did not stop the retina from continuing to degenerate. In another trial, 6 out of 9 patients with the degenerative disease choroideremia had improved vision after a virus was used to deliver a functional REP1 gene.

Credit: Jean Bennett, MD, PhD, Perelman School of Medicine, University of Pennsylvania; Manzar Ashtari, Ph.D., of The Children's Hospital of Philadelphia, Science Translational Medicine.

People with hemophilia are missing proteins that help their blood form clots. Those with the most-severe forms of the disease can lose large amounts of blood through internal bleeding or even a minor cut.

In a small trial, researchers successfully used an adeno-associated viral vector to deliver a gene for Factor IX, the missing clotting protein, to liver cells. After treatment, most of the patients made at least some Factor IX, and they had fewer bleeding incidents.

Patients with beta-Thalassemia have a defect in the beta-globin gene, which codes for an oxygen-carrying protein in red blood cells. Because of the defective gene, patients don't have enough red blood cells to carry oxygen to all the body's tissues. Many who have this disorder depend on blood transfusions for survival.

In 2007, a patient received gene therapy for severe beta-Thalassemia. Blood stem cells were taken from his bone marrow and treated with a retrovirus to transfer a working copy of the beta-globin gene. The modified stem cells were returned to his body, where they gave rise to healthy red blood cells. Seven years after the procedure, he was still doing well without blood transfusions.

A similar approach could be used to treat patients with sickle cell disease.

In 2012, Glybera became the first viral gene-therapy treatment to be approved in Europe. The treatment uses an adeno-associated virus to deliver a working copy of the LPL (lipoprotein lipase) gene to muscle cells. The LPL gene codes for a protein that helps break down fats in the blood, preventing fat concentrations from rising to toxic levels.

Several promising gene-therapy treatments are under development for cancer. One, a modified version of the herpes simplex 1 virus (which normally causes cold sores) has been shown to be effective against melanoma (a skin cancer) that has spread throughout the body. The treatment, called T-VEC, uses a virus that has been modified so that it will (1) not cause cold sores; (2) kill only cancer cells, not healthy ones; and (3) make signals that attract the patient's own immune cells, helping them learn to recognize and fight cancer cells throughout the body. The virus is injected directly into the patient's tumors. It replicates (makes more of itself) inside the cancer cells until they burst, releasing more viruses that can infect additional cancer cells.

A completely different approach was used in a trial to treat 59 patients with leukemia, a type of blood cancer. The patients' own immune cells were removed and treated with a virus that genetically altered them to recognize a protein that sits on the surface of the cancer cells. After the immune cells were returned to the patients, 26 experienced complete remission.

Patients with Parkinson's disease gradually lose cells in the brain that produce the signaling molecule dopamine. As the disease advances, patients lose the ability to control their movements.

A small group of patients with advanced Parkinson's disease were treated with a retroviral vector to introduce three genes into cells in a small area of the brain. These genes gave cells that don't normally make dopamine the ability to do so. After treatment, all of the patients in the trial had improved muscle control.

# data[].attributes.attachment_link.description
Researchers have been working for decades to bring gene therapy to the clinic, yet very few patients have received any effective gene-therapy treatments. But that doesn't mean gene therapy is an impossible dream. Even though gene therapy has been slow to reach patients, its future is very encouraging.

# data[].attributes.body
CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. It's a bacterial defense system which forms CRISPR-Cas9, a genenetic engineering technology.

# data[].attributes.attachment_link.readable_text
A: "CRISPR" (pronounced "crisper") stands for Clustered Regularly Interspaced Short Palindromic Repeats, which are the hallmark of a bacterial defense system that forms the basis for CRISPR-Cas9 genome editing technology. In the field of genome engineering, the term "CRISPR" or "CRISPR-Cas9" is often used loosely to refer to the various CRISPR-Cas9 and -CPF1, (and other) systems that can be programmed to target specific stretches of genetic code and to edit DNA at precise locations, as well as for other purposes, such as for new diagnostic tools. With these systems, researchers can permanently modify genes in living cells and organisms and, in the future, may make it possible to correct mutations at precise locations in the human genome in order to treat genetic causes of disease. Other systems are now available, such as CRISPR-Cas13's, that target RNA provide alternate avenues for use, and with unique characteristics that have been leveraged for sensitive diagnostic tools, such as SHERLOCK.
Q: Where do CRISPRs come from?
A: CRISPRs were first discovered in archaea (and later in bacteria) by Francisco Mojica, a scientist at the University of Alicante in Spain. He proposed that CRISPRs serve as part of the bacterial immune system, defending against invading viruses. They consist of repeating sequences of genetic code, interrupted by "spacer" sequences - remnants of genetic code from past invaders. The system serves as a genetic memory that helps the cell detect and destroy invaders (called "bacteriophage") when they return. Mojica's theory was experimentally demonstrated in 2007 by a team of scientists led by Philippe Horvath.

In January 2013, the Zhang lab published the first method to engineer CRISPR to edit the genome in mouse and human cells.

For more on many of the scientists and teams who contributed to the understanding and development of the CRISPR system from the initial discovery to the first demonstrations of CRISPR-mediated genome editing, visit our CRISPR timeline.
Q: How does the system work?
A: CRISPR "spacer" sequences are transcribed into short RNA sequences ("CRISPR RNAs" or "crRNAs") capable of guiding the system to matching sequences of DNA. When the target DNA is found, Cas9 - one of the enzymes produced by the CRISPR system - binds to the DNA and cuts it, shutting the targeted gene off. Using modified versions of Cas9, researchers can activate gene expression instead of cutting the DNA. These techniques allow researchers to study the gene's function.

Research also suggests that CRISPR-Cas9 can be used to target and modify "typos" in the three-billion-letter sequence of the human genome in an effort to treat genetic disease.

An artist's depiction of the CRISPR system in action.
Illustration by Stephen Dixon
Q: How does CRISPR-Cas9 compare to other genome editing tools?
A: CRISPR-Cas9 is proving to be an efficient and customizable alternative to other existing genome editing tools. Since the CRISPR-Cas9 system itself is capable of cutting DNA strands, CRISPRs do not need to be paired with separate cleaving enzymes as other tools do. They can also easily be matched with tailor-made "guide" RNA (gRNA) sequences designed to lead them to their DNA targets. Tens of thousands of such gRNA sequences have already been created and are available to the research community. CRISPR-Cas9 can also be used to target multiple genes simultaneously, which is another advantage that sets it apart from other gene-editing tools.
Q: How does CRISPR-Cpf1 differ from CRISPR-Cas9?
CRISPR-Cpf1 differs in several important ways from the previously described Cas9, with significant implications for research and therapeutics.

First, in its natural form, the DNA-cutting enzyme Cas9 forms a complex with two small RNAs, both of which are required for the cutting activity. The Cpf1 system is simpler in that it requires only a single RNA. The Cpf1 enzyme is also smaller than the standard SpCas9, making it easier to deliver into cells and tissues.

Second, and perhaps most significantly, Cpf1 cuts DNA in a different manner than Cas9. When the Cas9 complex cuts DNA, it cuts both strands at the same place, leaving 'blunt ends' that often undergo mutations as they are rejoined. With the Cpf1 complex the cuts in the two strands are offset, leaving short overhangs on the exposed ends. This is expected to help with precise insertion, allowing researchers to integrate a piece of DNA more efficiently and accurately.

Third, Cpf1 cuts far away from the recognition site, meaning that even if the targeted gene becomes mutated at the cut site, it can likely still be re-cut, allowing multiple opportunities for correct editing to occur.

Fourth, the Cpf1 system provides new flexibility in choosing target sites. Like Cas9, the Cpf1 complex must first attach to a short sequence known as a PAM, and targets must be chosen that are adjacent to naturally occurring PAM sequences. The Cpf1 complex recognizes very different PAM sequences from those of Cas9. This could be an advantage in targeting, for example, the malaria parasite genome and even the human genome.
Q: What other scientific uses might CRISPR have beyond genome editing?
A: CRISPR genome editing allows scientists to quickly create cell and animal models, which researchers can use to accelerate research into diseases such as cancer and mental illness. In addition, CRISPR is now being developed as a rapid diagnostic. To help encourage this type of research worldwide, Feng Zhang and his team have trained thousands of researchers in the use of CRISPR genome editing technology through direct education and by sharing more than 40,000 CRISPR components with academic laboratories around the world.