With CRISPR poised to revolutionise therapy, a pause to consider ethical issues

Subject: Science and tech

Section: Biotech

What is CRISPR?

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats.
CRISPR-Cas9 is the most prominent technology that enables to edit parts of the genome by removing, adding or altering sections of the DNA sequence.
The CRISPR-Cas9 system consists of two key molecules that introduce a change mutation into the DNA.
Cas9- An enzyme that acts as a pair of ‘molecular scissors’ that can cut the two strands of DNA at a specific location in the genome.
Guide RNA (gRNA)- The gRNA is designed to find and bind to a specific sequence in the DNA.
The Cas9 follows the guide RNA to the same location in the DNA sequence and makes a cut across both strands of the DNA.
At this stage, the cell recognises that the DNA is damaged and tries to repair it.
The DNA repair machinery is used to introduce changes to one or more genes in the genome of a cell of interest.
The technology replicates a natural defence mechanism in some bacteria that uses a similar method to protect itself from virus attacks.

What are the advantages of this technology?

Faster and Cheaper– It is faster and cheaper than previous techniques of editing DNA.
High accuracy– Genetic engineering has made the work more accurate by allowing scientists to have greater control on trait development.
Viable compared to GMO- CRISPR technology proves viable against the criticisms of Genetically Modified Organisms (GMO).

Gene Therapies to Treat Sickle Cell: Lyfgenia

Process Involved: It uses a disabled lentivirus as a vector to introduce into the blood stem cells a new gene for hemoglobin same as the healthy gene.
Achievement: In clinical trials, 30 of 32 sickle cell disease patients did not suffer from severe blocked blood flow caused by sickle cells, while 28 of 32 patients did not experience any blocked blood flow events six to 18 months post-infusion.

Casgevy:

Process Involved: It uses the gene-editing tool of CRISPR-Cas9 to disable a particular gene (BCL11A) that turns off fetal hemoglobin production in blood stem cells.
- By disabling the BCL11A gene, the produced fetal hemoglobin does not have the abnormalities of adult hemoglobin, hence, helps to treat patients with sickle-cell disease or beta thalassaemia.
Achievement: In clinical trials, 28 of 29 sickle-cell disease patients who received Casgevy gene therapy were relieved from the disease for a year.
- For beta thalassaemia, 39 of 42 patients did not require blood transfusion for one year, and in the remaining three the need for blood transfusion reduced by more than 70%.

What are the issues with CRISPR technology?

Ethical concerns– In 2018, a Chinese researcher’s disclosure of creating a ‘designer baby’ has caused widespread concern in the scientific community.
Biological concerns– Though the technology is not 100% precise and has the risk of causing mutations, side effects and undesirable changes like antibiotic resistance.
Genetic drive – Once the manipulated genes get transferred on to next generations, they become part of the environment.
Gene gap– CRISPR can be very expensive and get limited to those who can afford it.

Where does India stand in the field of gene editing and CRISPR?

India is at its infancy when it comes to genome editing.
Research in gene editing is not so abundant but it is growing steadily.
Although the funding for biology has been steadily growing, a lot of investment is needed in infrastructure.
India’s draft gene-editing rules allows genome-edited organisms without any “foreign” genes to be subjected to a different regulatory process than the one applied to genetically engineered products.