CRISPR/Cas9- Genome editing

CRISPR technology is reshaping genetics as we know it, moving us onto a new level of personalised medicine. 

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1.What is it?

CRISPR – Clustered Regularly Interspaced Short Palindromic Repeats

CRISPR/ Cas9 is a DNA phage- enzyme complex which can remove and insert genetic material with high specificity and sensitivity, as a complex exclusive to the target genetic code.

The technology is currently only being tested on somatic disorders to prevent alterations affecting future generations. This helps with regulation as we anticipate the effects of gene therapy. 

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Credit- iStock/Meletios Verras

2. Why is it important?

Genetics research is constantly finding genetic components to many diseases. To date, the Online Mendelian Inheritance in Man database, OMIM, holds a staggering record of 24, 608 monogenic diseases.

These take into account autosomal, X linked, Y linked and mitochondrial mutations which include the following:

  • Cystic fibrosis
  • Sickle cell anaemia
  • Beta thalessemia
  • Huntington’s disease
  • Phenylketonuria 
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OMIM overall statistics

These statistics put into perspective the potential impact CRISPR- Cas9 technology can have on monogenic diseases alone which millions of people suffer from worldwide.

3. How does it work¹?

CRISPR repeats are small parts of viruses found in bacterial DNA which detect the same molecular pattern on further incoming foreign viruses. This activates the production of an enzyme, Cas9, which has been dubbed by the name “molecular knife” and cuts out the identified section of viral DNA. The result: altered protein production to dampen the effects of the viral infection. 

The integration to human genetics:

  1. Use primer RNA: Cas9 compound to find the target DNA sequence
  2. Primer RNA pairs up with associated DNA sequence
  3. Cas9 cuts the target DNA
  4. A break is created in both strands of the DNA sequence
  5. DNA ligase as repair enzymes repair the break

Result: edited DNA sequence which prevents the protein production to a specifically targeted genetic disorder, hence curing the patient. 

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Three stages of CRISPR/ Cas9 immunity (Ref 2)

4. The future

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There is also a programme, Safe Genes, being designed to regulate gene therapy bioerrors and bioterros to enable us to retract changes to the original vector and reverse damages in order to have better control.

5. Who is involved?

Feng Zhang – MIT, Cambridge; Zhang Lab

UK- Francis Crick Institute, London 

DARPA- Safe Genes database 

Overall, there are currently thousands of scientists around the working working on this technology but some of the most renown labs include:

References:

1. Xu X, Duan D, Chen S. CRISPR-Cas9 cleavage efficiency correlates strongly with target-sgRNA folding stability: from physical mechanism to off-target assessment. Scientific Reports. 2017;7(1).

2. Amitai G, Sorek R. CRISPR–Cas adaptation: insights into the mechanism of action. Nature Reviews Microbiology. 2016;14(2):67-76.

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