Gene editing Technology Current Affairs

REPAIR: Scientists develop RNA editing tool to combat genetic disease

Scientists from The Broad Institute and Massachusetts Institute of Technology in US have developed RNA Editing for Programmable A to I Replacement (REPAIR), a new gene editing tool therapies that can reverse disease-causing mutations in humans.

REPAIR gene editing tool can tweak an individual RNA ‘letters’ in human cells without making changes to entire genome  and can have profound potential as a tool for both research and disease treatment.

REPAIR

REPAIR is based on gene editing tool CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) that can be used to modify DNA in cells. The new tool can change single RNA nucleosides in mammalian cells in a programmable and precise fashion.

To create REPAIR, scientists had systematically profiled CRISPR-Cas13 enzyme family for potential editor candidates. They had selected enzyme called PspCas13b from Prevotella bacteria which was most effective at inactivating RNA.

Scientists had engineered deactivated variant of PspCas13b enzyme that binds to specific stretches of RNA but lacks its scissor-like activity and fused it to a protein called ADAR2, which changes nucleoside adenosine to inosine in RNA transcripts.

Significance

REPAIR has ability to reverse disease-causing mutations at RNA level, as well as other potential therapeutic and basic science applications. It paves way for therapies that can reverse mutations and has profound potential as tool for both research and disease treatment.

REPAIR has ability to target individual RNA letters or nucleosides, switching adenosines to inosines. These letters are involved in single-base changes which are known to regularly cause genetic disease in humans. For ex, in human disease, a mutation from G to A is extremely common and these alterations have been implicated in for cases of focal epilepsy, Parkinson’s disease and Duchenne muscular dystrophy.

Thus, it can reverse impact of any pathogenic G-to-A mutation regardless of its surrounding nucleotide sequence, with potential to operate in any cell type.

Comment

RNA editing using REPAIR offers safer, more flexible way to make corrections in cell unlike permanent changes to genome required for DNA editing using CRISPR-Cas9 gene editing technology. REPAIR can also fix mutations without tampering with genome as RNA naturally degrades making it potentially reversible fix.

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First human genetic editing trial in China

Chinese scientists are going to perform the world’s first genetic editing trial on humans in an attempt to find a cure for lung cancer.

It will be performed as the trial phase by injecting cells that have been modified using the CRISPR-Cas9 gene-editing technique into the patients.

Key Facts

  • In this trial, scientists will extract T cells, a type of immune cell, from the patient’s blood.
  • Then they will put the gene that encodes the PD-1 protein, which normally limits the cell’s capacity to launch an immune response.
  • The edited cells will be allowed to multiply in the lab before being reintroduced to the patients. This process will kick-start the T cells to launch an attack on the tumour cells.
  • This method is like building a cancer-fighting army outside the patient body. However the only concern is that T cells might also attack normal tissue.

What is CRISPR-Cas9 gene-editing technique?

  • CRISPR short form of clustered regularly interspaced short palindromic repeats. It allows scientists to selectively edit genome parts and replace them with new DNA stretches.
  • Cas9 is an enzyme that can edit DNA, allowing the alteration of genetic patterns by genome modification. CRISPR is a collection of DNA sequences that direct Cas9 where to cut and paste.
  • CRISPR-Cas9 technology has the potential to revolutionise the treatment of blood diseases, tumours and other genetic diseases.

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