Innovative tool offers hope for children with rapid-aging disease progeria

Good news! This may well be another great breakthrough for genetic base editors like CRISPR! This new gene editing method may also be applicable to other genetic diseases! However, it may take a while to safely transfer this new treatment from mice to humans!

"... a team of scientists from the Broad Institute of MIT and Harvard ..., the National Institutes of Health, and Vanderbilt University Medical Center to achieve an almost unbelievable leap for the CRISPR gene-editing tool known as base editing, moving the technology a critical step closer to being a treatment for progeria, a deadly premature aging disease. Several hundred children worldwide live with the malady. In most cases, just one small error involving one of the four main bases, or building blocks, of DNA — a thymine (T) in place of a cytosine (C) at one position in just one copy of the lamin A gene in a cell nucleus — causes the body to produce a toxic protein known as progerin. ... used an adenine base-editing treatment in mice to successfully convert an impressive percentage of those errant Ts back to Cs in DNA, RNA, and protein, leading to a dramatic improvement in tissue health (including the heart) and lifespan — mice lived about 2½ times longer with just a single treatment and reached the start of what would be old age in normal, healthy mice. ... Because their effort proved so successful, the work not only offers a path to treat progeria, it provides a blueprint for testing novel gene-editing treatments for other genetic diseases like sickle cell anemia and muscular dystrophy. ...
“To our knowledge, this work resulted in the strongest rescue of the symptoms of progeria by multiple measures,” he continued. “Five years ago, we were still finishing the development of the very first base editor. If you had told me then that within five years, a single dose of a base editor could address progeria in an animal at the DNA, RNA, protein, vascular pathology, and lifespan levels, I would have said, ‘There’s no way.’ ...
Since about half of all known disease-causing mutations are single-letter errors (like progeria), other scientists could use this study as a guide to hone base editors to cure more genetic disorders in humans. ...
While the team observed no significant off-target edits, some of the longest-living mice developed liver tumors, a known complication when using adeno-associated viruses (AAVs) to deliver genes into mice that are allowed to live into old age. ..."

"Hutchinson–Gilford progeria syndrome (HGPS or progeria) is typically caused by a dominant-negative C•G-to-T•A mutation (c.1824 C>T; p.G608G) in LMNA, the gene that encodes nuclear lamin A. This mutation causes RNA mis-splicing that produces progerin, a toxic protein that induces rapid ageing and shortens the lifespan of children with progeria to approximately 14 years ...Lentiviral delivery of the ABE [Adenine base editor] to fibroblasts from children with HGPS resulted in 87–91% correction of the pathogenic allele, mitigation of RNA mis-splicing, reduced levels of progerin and correction of nuclear abnormalities. ..."

Innovative tool offers hope for children with rapid-aging disease Progeria study finds base-editing therapy more than doubles the lifespan of mice

Here is the underlying research article:

In vivo base editing rescues Hutchinson–Gilford progeria syndrome in mice (behind paywall)