Bengaluru: Scientists in the US claim to have cured progeria in mice with the help of gene-editing techniques.
Progeria is a rare but fatal genetic disease that rapidly accelerates ageing in children, giving them a lifespan of 14 years on average. The condition, which doesn’t have a cure yet, was portrayed by actor Amitabh Bachchan in the Bollywood movie Paa.
The Harvard-led study, also involving Vanderbilt University and the US government’s National Institutes of Health, aimed to treat the specific mutation in the genome that produces progerin, a toxic protein that induces rapid ageing and shortening of lifespan.
The researchers used a technique called base editing, which was originally inspired by the gene-editing technology CRISPR, to edit out a single base or one of the four letters of the DNA.
In a study published in the journal Nature last week, the scientists said their findings confirmed progeria was cured in mice.
Base editing vs CRISPR
DNA is made up of four nucleotides, or nitrogenous organic molecules that serve as its building blocks. These are the bases for the DNA and are indicated by letters: cytosine (C), guanine (G), thymine (T), and adenine (A).
These four bases build up the double-helical DNA in the form of pairs, commonly known as base pairs.
The CRISPR-Cas9 technique makes double-stranded cuts in DNA, but most human diseases are caused by errors in single DNA nucleotides. These are called ‘point mutations’.
Researchers have identified over 31,000 point mutations that cause genetic diseases in humans. However, CRISPR is not efficient at correcting these.
Instead, inspired by CRISPR, the researchers involved in the progeria study had devised a new technique called base editing. This technique uses a new class of genome-modifying proteins that can fix single-site point mutations.
Base editors modify DNA bases by changing one base or one letter to another without completely affecting the DNA structure or making double-stranded breaks in the structure. As a result, they are believed to have more efficiency than CRISPR for treating genetic diseases in humans, and cause fewer errors.
CRISPR was previously used to treat progeria in mice, with only limited outcomes. But base editors have treated eye, ear, and brain disorders in mice before.
The researchers from NIH who tested the base-editing approach for progeria were also the ones who originally identified the progeria mutation in 2003.
The technique was first tested in vitro in cultured cells from progeria patients. The team found that they were able to correct the mutation but some other changes occurred in the genome as well.
They then switched to using an adenovirus associated vector, very similar to the one used in Oxford-AstraZeneca Covishield vaccine, as a standard, tested delivery vector, and injected mice with progeria.
Six months later, the team said, 20 to 60 per cent of these mices’ bones, muscles, and blood was carrying the edited, fixed DNA. The researchers noticed a sharp drop in progerin. Weeks later, they added, they discovered that the mices’ bodies bore no signs at all that tissues and organs had suffered damage by progeria.
The researchers are working on launching a clinical trial in children in the near future.