A treatment that lowers bad cholesterol for 3 years Gene editing therapy demonstrates long-term efficacy and safety

A recent study published on Therapy provides preliminary answers to both questions.
study, conducted by Gene Therapy pioneer Professor James M. Wilson of the University of Pennsylvania and his co-researchers, edited the PCSK9 gene for non-human primates.
study found that single-use gene editing significantly reduced PCSK9 protein and low-density lipoprotein cholesterol (LDL-C) levels in animals and lasted for up to three years.
researchers also found no significant adverse reactions.
PCSK9 is an important target for reducing LDL-C, and several antibody therapies targeting PCSK9 and one RNAi therapy have been approved for the market.
, the use of gene-editing therapy to turn off PCSK9 expression at once, thereby permanently reducing the risk of cardiovascular disease in patients is becoming an emerging development direction.
, Verve Therapeutics announced that its CRISPR-based gene-editing therapy, VERVE-101, could consistently lower LDL-C levels for the next six months after a treatment in non-human primate experiments.
Sekar Kathiresan, ceo of the company, said at the 2021 Drug Mingkang Global Forum that the key to applying this treatment to a wide range of cardiovascular patients is to demonstrate the durability and safety of the treatment.
study, published in Molecular Therapy, researchers used the ARCUS genome editing technology platform developed by Precision BioSciences.
this is a genome editing platform based on a natural home-to-nest cutase called I-CreI.
this endoenzyme belongs to a wide range of meganucleases.
It does the cutting by identifying a sequence of targets containing 22 bases, and because the target sequence is long, there is little chance of off-target editing, and after editing, it automatically loses life, further reducing the risk of off-target editing.
addition, its other advantage is that it has a small head, with only 364 amino acids, making it easier to deliver to tissues or cells using viral or non-viral delivery methods.
the experiment, the researchers used AAV vectors to deliver arcus gene editing systems targeting the PCSK9 gene to the livers of non-human primates.
have been observed for more than three years after undergoing gene editing therapy.
the results showed that PCSK9 protein levels in genetically edited animals continued to decrease by 85%, while LDL-C levels continued to decrease by 56%.
Over a three-year period, liver cells have undergone several iterations, and these results mean that gene editing changes to the genome are passed on to a new generation of liver cells, and the reductions that support PCSK9 and LDL-C levels are permanent.
also important, histological studies of the animal liver did not find significant adverse changes, and the frequency of off-target editing remained at very low levels.
" study shows that gene editing in the body using a dose of ARCUS system can have long-lasting therapeutic effects, and it provides critical safety data to support clinical transformation studies.
" Dr. James Wilson said, "This study not only accumulates evidence for the development of gene editing as a potential treatment, but also suggests that the ARCUS gene editing system could be a very promising new strategy for treating patients with cardiovascular disease."
" Previously, at the 2021 Pharmaceuticals Global Forum, the CEOs of several cell and gene therapy start-ups had come to the consensus that we had made significant progress in researching and interpreting the genome over the past 20 years, and that humans would rewrite the genome for health over the next 20 years.
this research has taken us one step closer to that goal.
: s1. Precision Announces 3-Year Pre-clinical Study Results Show Long-term Durability and ARCUS In Vivo Gene Editing to Cut LDLCholesterol Levels in Nonhuman Primates. Retrieved February 19, 2021, from [2] Precision Biosciences. Retrieved February 19, 2021, from [3] Wang et al., (2021). Long-term Stable Reduction of Low-density Lipoprotein in Nonhuman Primates Following In Vivo Genome Editing of PCSK9. Molecular Therapy,