Breakthrough for sickle cell anaemia: How this home-grown gene editing tool can make therapy cheaper, effective

With the therapy — as well as the platform it is based on and many of the reagents used in the process — being indigenously developed, the treatment is likely to cost just a fraction of what the therapy approved a couple of years ago costs. The gene therapy Casgevy costs around USD 2.2 million.

“The researchers from IGIB came up with the idea to develop an indigenous CRISPR system in 2016. The IP for the one used in the West is very costly — we needed to develop our own to bring down the cost of gene therapies. The proof of concept was developed over the next six years. The potential of the platform was immediately realised by the ministry of tribal affairs — and the therapy for sickle cell disease was developed,” said Dr Souvik Maiti, director, IGIB.

The researchers — along with the team from Serum Institute of India — are also working to develop a therapy for thalassaemia using the same tool.

How does Birsa-101 cure sickle cell disease?

Sickle cell disease is a genetic condition that leads to the body’s red blood cells becoming rigid, sickle-shaped, and less capable of carrying oxygen. The shape of the blood cells can also lead to blockages in blood flow, leading to acute episodes of pain, chronic pain, organ damage, anaemia, infections, and strokes. A person can be a carrier and not have a disease. The likelihood of a child having the disease increases if both parents are carriers or one parent has the disease and the other is a carrier.

To cure the condition, Birsa-101 precisely corrects the mutations in the genetic code that causes the disease. The therapy has to be given as a one-time infusion, after which the body should start producing normal red blood cells instead of sickle-shaped ones.

This method is very different from the globally approved treatment Casgevy, which edits a gene to push the body’s blood manufacturing mechanism to make more foetal haemoglobin, which does not carry the same defect. Foetal haemoglobin, which is naturally present in everyone at birth, does not carry the same abnormalities as adult haemoglobin. The same therapy can be used for the treatment of thalassaemia — another inherited blood disorder where the body produces little or no haemoglobin.

The thalassemia therapy, which is being developed by IGIB and SII, will also use the same mechanism.

How does the gene therapy tool developed by IGIB work?

The CRISPR Cas9 gene editing tool — the genetic scissors that won the 2020 Nobel Prize in Chemistry — is essentially based on proteins from the immune system of bacteria which can shred genetic material. These proteins can be harnessed to specifically cut out damaged genetic material.

“Now, the number of Cas9 proteins is huge — they are present in nearly 50% of all bacteria. The problem is that most of them cannot be used because of a phenomenon called off-targeting, where the genetic material gets edited at other places in addition to the intended edit. This can be devastating,” said Dr Debojyoti Chakraborty, senior scientist who heads the research at IGIB.

Explaining, he added: “What we have done is look for Cas9 proteins that are highly specific, meaning they would not affect genes other than the ones being targeted. These were, however, not very effective. We engineered them to increase efficacy.”

The tool has been transferred to SII on a non-exclusive basis, meaning other companies can also utilise it for developing other therapies.

What is the need for the treatment?

If found to be effective in curing sickle cell disease, the therapy will first be offered to those with severe disease, perhaps with organ damage. And, may later be expanded to children.

An estimated 30,000-40,000 children in India are born with the disorder every year.

The government has also launched a mission with the aim of eliminating the disease by 2047, mainly by screening carriers of the gene and making them aware of the risk of having a child with other carriers.