Integrated’s AI platform to discover senolytic compounds; plus Editas’ transgene knock-in method and more

Integrated Biosciences Inc. and the Broad Institute of MIT and Harvard researchers screened 2,352 compounds for senolytic activity and trained neural networks to predict the senolytic activity of more than 800,000 molecules. In a Nature Aging paper, researchers including Integrated co-founder Felix Wong identified three drug-like compounds that selectively target senescent cells, acting in part by inhibiting apoptosis regulator BCL-2. One compound, BRD-K56819078, decreased senescent cell burden and mRNA expression of senescence-associated genes in the kidneys of aged mice.

Editas Medicine Inc. (NASDAQ:EDIT) presented in Nature Biotechnology a CRISPR nuclease that targets a site within an exon of an essential gene and designed a cargo template that restores the essential gene coding sequence while incorporating the transgene(s) of interest. The authors showed the method, dubbed SLEEK (SeLection by Essential-gene Exon Knock-in), led to knock-in efficiencies of more than 90% in induced pluripotent stem cells (iPSCs) using a plasmid DNA template; between 85% and 95% in B cells, T cells and NK cells using AAV6 DNA templates; and is over 100-fold more potent than AAV6 knock-in at the conventional TRAC locus...