By Faisal Khan | 4 August 2022
CRISPR-based treatments have evolved significantly in the last few years. Not only have we seen higher efficacy in treating various genetic conditions, but molecular scissors have also continued to evolve towards improving the technique. Earlier last month, I talked about a fine-tuned CRISPR-Cas9 gene editor — one which significantly reduces the chance of potentially harmful mutations.
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— Faisal Khan (@fklivestolearn) July 12, 2022
To keep this innovation going, researchers have moved ahead from the conventional approach of the CRISPR-Cas9 editor, which slices right through the entire double strand of DNA. The CRISPR ‘cousin’ that we are talking about today makes single-letter changes to a DNA sequence — the base editing technique involved in the novel trial makes changes to a cholesterol-regulating gene without breaking both strands of DNA first.
Since it was first developed in 2016, multiple base editors have been designed to alter DNA in different ways — albeit with higher efficiency, with a reduced occurrence of genetic mutations. As the current trial progresses, other potential base-editing treatments are working their way through the pipeline to similar trials.
A recent #clinicaltrial has explored the safety and efficacy of #baseediting, a #genomeediting method related to the #CRISPRCas9 system, to make precise, single-letter changes to a #DNA sequence in a cholesterol-regulating gene.
— GenScript (@GenScript) July 19, 2022
The current two trials are expected to report results in 2023. The first one involves changes to a DNA sequence in a cholesterol-regulating gene, whereas the second one is expected to treat a participant suffering from the sickle-cell disease — a genetic blood disorder. Both these tests are expected to pave the way for more efficient and safer therapies in the future.
“It’s very exciting that the first clinical trials are starting, with CRISPR–Cas9 and now also with base editing. We’ve got a lot to learn.”
~ Gerald Schwank, University of Zurich
According to the approach developed by Verve Therapeutics in Cambridge, Massachusetts (USA), the first trial would involve a base editor to convert an adenine base (A) to a guanine one (G) in the DNA encoding a protein called PCSK9 — a key regulator of blood cholesterol levels. The process involves reducing the amount of functional PCSK9, thus reducing the chance of high cholesterol, which ultimately leads to heart disease.
Many of the researchers who have looked at the technique are optimistic about what it could achieve. However, they would be keenly looking at the benefits of the treatment, and whether they outweigh the side effects if any. The Verve trial (first one) aims to edit cells directly in the body via lipid nanoparticles — similar to ones used on mRNA COVID-19 vaccines.
The sickle-cell trial will use base editing to alter DNA in blood stem cells that have been removed from the body, before being reinfused into the patient. This trial would be conducted by Beam Therapeutics. As these promising trials progress, other base-editing therapies treat conditions like leukemia; a rare metabolic condition called glycogen storage disease, and Stargardt’s disease; which can cause blindness, are being developed.
Reprinted with permission from the author.
Faisal Khan is a prolific Canada-based tech blogger and influencer. He is the founder and editor of the Technicity publication which focuses on technical, scientific and financial knowledge sharing. Follow him on Twitter @fklivestolearn.
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