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Milestone: The first CRISPR gene editing study for patients was published in NEJM, and the Nobel Prize winner developed
The First CRISPR gene editing study for patients was published in NEJM. On June 26, 2021, the New England Journal of Medicine (NJEM) published a research paper “CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis” by Professor Gillmore of University College London, UK. Amyloidosis (ATTR)).
The results show that the CRISPR gene editing therapy NTLA-2001 jointly developed by Intellia Therapeutics and Regeneron of the United States has achieved very exciting results in a phase 1 clinical trial for the treatment of ATTR patients; this is also the first human CRISPR. Clinical trials on the safety and effectiveness of gene editing.
For this milestone research progress, various medical and biological media are extremely praised. This is the latest and crucial step in applying CRISPR gene editing technology to treat human genetic diseases.
del Aguila III, Ernesto. (2018). “CRISPR Cas9” [Illustration]. Retrieved from Flickr.
After a single dose of 0.3 mg/kg of NTLA-2001 treatment, the level of transthyretin (TTR) in the serum of ATTR patients decreased by an average of 87%, and the TTR decreased by up to 96% on the 28th day; and there is a dose
By the 28th day, no serious adverse events were observed in the 6 patients treated.
NTLA-2001 therapy and ATTR disease
NTLA-2001 is the first CRISPR-Cas9-based innovative therapy to be administered systemically by intravenous infusion. It uses lipid nanoparticles (LNP) to package a CRISPR gene editing system that targets the TTR gene.
(Mechanism of action. Source: NEJM)
Transthyretin amyloidosis (ATTR) is a rare, progressive and fatal disease. It affects about 50,000 patients worldwide, and the prognosis is poor. Most patients expect to live only 2-15 years from the appearance of symptoms.
From a clinical point of view, transthyretin (TTR) is a protein produced by the liver that carries thyroid hormone and vitamin A in the blood. However, in ATTR patients with amyloidosis, proteins become unstable, decomposed and deposited in organs such as the heart, peripheral nerves, kidneys, gastrointestinal tract and eyes; clinically, ATTR cardiomyopathy (ATTR-CM) and ATTR multiple Neuropathy (ATTR-PN) is the main clinical manifestation.
(Photo source: Cleveland Clinic, USA)
From the perspective of pathogenesis, specific mutations in the TTR gene in ATTR patients cause the liver to produce misfolded transthyretin. The protein will accumulate in multiple tissues throughout the body and cause ATTR amyloidosis; with the accumulation of amyloid fibers, tissues and organs may not work properly, and this can lead to fatal complications.
NTLA-2001 specifically knocks out the TTR gene in liver cells to prevent the production of misfolded transthyretin (TTR), thereby achieving the purpose of treatment.
(Photo source: Cleveland Clinic, USA)
Although the U.S. Food and Drug Administration (FDA) has approved Pfizer’s drugs for the treatment of ATTR-CM in 2019, the current treatment requires daily and lifelong treatment.
By knocking out disease-causing genes, NTLA-2001 may reverse the disease through a single treatment, that is, it has the potential to cure ATTR with one treatment.
In addition to the landmark innovation of this research, Intellia Therapeutics is also attracting attention. One of its co-founders is Professor Jennifer Doudna. Doudna won the 2020 Nobel Prize in Chemistry together with Professor Emmanuelle Charpentier for his contribution to the CRISPR gene editing system.
The revolutionary discovery of CRISPR is and will continue to rewrite the treatment of human diseases。
(source:internet, reference only)