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1. HLA-B27 gene is present in white blood cells => When CRISPR-Cas9 is used to edit the somatic cells, will it be cured permanently?

2. Since it is used to edit the somatic cells and not germ line cells, will the change be present in the cells of the children? (Maybe not).

Evaluation of gene editing technology as possible treatment option:

(+) Can edit genes that are correlated with the disease: (mainly) HLA-B27, ARTS1 and IL23R

(+) Or can edit genes that help for treatment: Improve effectiveness of adalimumab (TNF inhibitor) => optimise molecular targets of such drugs

(-) AS also has environmental causal factors

(-) Less practical research/thorough experiments done yet

(-) Somatic VS Germ line cell editing

(-) Ethical concerns?

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https://scitales.ccmb.res.in/will-i-be-healthy-can-genetic-testing-predict/

Read the above article.

Imagine the women suffering from ankylosing spondylitis visits you.

As a CRISPR-Cas9 expert, discuss with a partner how can the below queries be answered? Evaluate the gene editing technology against the metabolic and cellular process of the body to provide a response to the patient.

- Now that I know the risk genes, can it be cured?

- If I get cured, does that erases the risk of the disorder in any of my future children too?

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Her children has a 50% chance of developing it but the gene doesn't guarantee that it would develop as a child. Also, environmental factors should be considered as it can trigger infections.

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There will be a lower risk.

If only HLA-B27 gene is removed using CRISPR-Cas9 then there will be a lower risk of her daughter having the disorder.

Steps :
1. The HLA-B27 gene (target sequence) is identified as the segment of DNA associated with certain autoimmune diseases.

2. The gRNA ensures specificity by binding only to the desired target region.

3. The Cas9 enzyme (a nuclease) binds to the guide RNA, forming a complex. This complex can recognize and bind to the matching DNA sequence in the genome.
4. Once the gRNA pairs with the complementary sequence in the HLA-B27 gene, Cas9 is activated and breaks the DNA.
5. The cell attempts to repair the break. This repair process can create insertions, deletions or substitution

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Q1) I believe it can, CRISPR cas-9 has the ability to simultaneously edit multiple genes.

Q2) Usually this type of therapeutic gene editing typically somatic cells leaving the reproductive cells like the sperm and egg untouched. This means that even if a woman cures her specific genetic disease it does not mean that it erases the risk of the disorder in her children too. These changes could be heritable by this type of editing which edits germline cells which is still in research.

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CRISPR - Cas9 could possibly edit the HLA-B27 gene to prevent the misfolding protein that triggers the inflammation.

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Question 1: Since we are aware of the genes responsible for the condition, there's definitely scope for CRISPR-Cas9 gene editing to be a preventative measure for ankylosing spondylitis. However, there are also other functions which the genes that cause the illness are responsible for, for example, HLA B27 is responsible for initiating an immune response in certain cells and helping the body differentiate between foreign and somatic cells, thus, it's removal would eliminate a critical component of immune surveillance. Hence, although it's theoretically possible for CRISPR to be used for this condition by editing genes in the somatic cells of the spinal cord, there are quite a few side effects to be taken into account.

Question 2: Editing of the somatic cells doesn't ensure that the changed genes are not present in the reproductive cells (sperm or ova). Hence, even if CRISPR is used and it reduces your risk to get the illness, it doesn't ensure that the risk would be reduced for your children.