prouesse medicale crispr in vivo traitement unique couv

Gene editing could happen directly inside the body thanks to CRISPR

#Gene #editing #happen #body #CRISPR

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Ten years after its discovery, CRISPR continues to amaze and is becoming increasingly essential in therapies against genetic diseases. Recently, researchers reported conclusive results from a clinical trial with CRISPR Live, with the aim of inactivating a gene involved in angioedema. A single injection of CRISPR into the blood of three people with this rare genetic disease alleviates their symptoms and allows them to live without medication for life. A feat that paves the way for promising future treatments.

CRISPR is a powerful tool for genome editing, which means that it allows researchers to easily alter DNA sequences and change the function of genes. It has many potential applications, including correcting genetic defects, treating and preventing the spread of disease, and improving the growth and resistance of cell cultures in the laboratory.

You should know that “CRISPR” is short for “CRISPR-Cas9”. CRISPRs are specialized DNA segments and the Cas9 protein is an enzyme that acts like a pair of molecular scissors, capable of cutting DNA strands.

CRISPR has already been shown to treat blood disorders through a strategy ex-vivo in which a patient’s cells are collected, edited in the lab, and then returned to the body. An approximation Live for blindness disorders, where the gene editor is injected into the eye, it also shows temporary benefits. But targeting CRISPR to specific organs or cells within the body via intravenous infusion is more difficult.

Recently, a team of researchers from Intellia Therapeutics, a biotech company working with the CRISPR tool, revealed a first in the medical world, an infusion of the gene editor CRISPR into the blood of three people with a rare genetic disease that actually alleviates Your symptoms. . This feat is the subject of an article published in the magazine Sciences.

A promising medical feat for the future

The data was reported at a meeting in Berlin on the disease, called hereditary angioedema. This effort marks the second time the company, Intellia Therapeutics, has used Live of CRISPR to inactivate a gene directly inside a person’s body. But the latest findings join the first report of clinical benefits associated with injecting the tool, which can cut or replace specific pieces of DNA, says John Leonard, president and CEO of Intellia, in an article related to the study. Jocelyn Kaiser.

In fact, last year, Intellia and its partner Regeneron reported that in people with a rare genetic condition called transthyretin amyloidosis (ATTR), a CRISPR drug Live stopped the buildup of liver proteins that can cause nerve pain, numbness, and heart problems.

Although the benefit appears to be long-lasting, the company has not yet disclosed whether patients’ symptoms have improved. For the hereditary angioedema trial, however, the benefits quickly emerged, Intellia reports.

You should know that this disease is the result of mutations that disable a protein called C1 esterase inhibitor, which is part of a signaling pathway that controls levels of bradykinin, a peptide hormone that causes fluid to leak into blood vessels . In people with hereditary angioedema, stress, illness, or trauma can trigger high levels of bradykinin in the blood, leading to severe swelling in the extremities, abdomen, or even the throat, which can cause the person to become drowned.

Medications can help prevent these attacks by blocking a protein, kallikrein, that increases bradykinin levels, essentially counteracting the effects of C1 esterase inhibitor loss. But CRISPR could allow patients to avoid the use of these drugs for life by permanently deleting the kallikrein gene. Specifically, Intellia has developed a DNA editing mechanism that involves a dual RNA structure that directs a Cas9 endonuclease to introduce specific cuts at the target site in the DNA. A strand of RNA guides them to the gene in question.

CRISPR Livea single injection effective for life?

in the article of SciencesJocelyn Kaiser explains that to provide the gene editor Live, the company wrapped this guide RNA and a messenger RNA that encodes the enzyme in a lipid nanoparticle. When injected into a patient’s bloodstream, the nanoparticles travel to the liver, where kallikrein is produced, and are attracted to cells there. They produce the enzyme CRISPR, which is transported to and cleaves the kallikrein gene.

In the hereditary angioedema trial, three patients who received a low dose of CRISPR treatment saw their blood kallikrein levels drop by an average of 65% at 8 weeks, reported clinical immunologist Hilary Longhurst at the 2022 Bradykinin Symposium. .three bouts of swelling per month she has had none since treatment and has not resumed medication. The third, who had much more frequent seizures, up to seven seizures per month, is now seizure-free after 10 weeks.

Kallikrein levels fell further, by 92%, in three patients more recently treated with a higher dose of CRISPR nanoparticles. These results suggest that the system is efficient, versatile, and programmable by modifying the DNA target-binding sequence in the guide RNA.

Emulation in medical research

Other teams are also testing gene editing. Live to treat various diseases. In July, the biotech company Verve Therapeutics began a clinical study of a new approach to managing cardiovascular disease with single-treatment gene-editing drugs. She is particularly interested in an inherited form of hypercholesterolemia caused by an overactive gene called PCSK9.

Sekar Kathiresan, MD, co-founder and CEO of Verve, explains in a press release: This is a first-in-class gene-editing drug that we have designed to make a single spelling change to the liver’s DNA to permanently disable the pathogenic gene. Dosing the first human with such an experimental base-editing drug represents a significant achievement for our team and for the field of gene editing. “. Preclinical data suggests, along with the Intellia treatment, that VERVE-101 has the potential to offer people with this disease a novel treatment option in a single injection.

Source: Science

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