BioCentury
ARTICLE | Translation in Brief

Matt Disney’s microRNA-targeting angiogenesis compound; Arrakis’ platform to find compounds’ RNA targets; dual target CAR Ts for HIV and more

BioCentury’s roundup of translational news

Scripps microRNA-targeted VEGF-A stimulator
A Scripps Research Institute team led by Matthew Disney has designed a compound that targets a  precursor of miR-377, a direct inhibitor of angiogenesis factor VEGF-A. Reported in a Nature Chemistry article, the researchers had identified the miR-377 precursor inhibitor by combining the output of their two-dimensional combinatorial screening method — which identifies RNA motif-small molecule binding partners — with data on RNA regulators of VEGF-A. They then optimized the compound and showed in human umbilical vein endothelial cells (HUVECs) that it reduced levels of mature miR-377, boosted VEGF-A mRNA levels and induced a pro-angiogenic phenotype. Disney is a founder of RNA-targeting small molecule play Expansion Therapeutics Inc. (see “Expanding Small Molecule Horizons”).

Arrakis’ platform to identify drug targets
In an ACS Chemical Biology paperArrakis Therapeutics Inc. described the use of its PEARL-seq technology to identify the RNA sequences targeted by small molecules and reveal information about ligand selectivity. In a proof-of-concept experiment, the company used PEARL-seq to confirm the RNA-binding site of a compound it had identified via a DNA-encoded library screen. Arrakis, which is developing RNA-binding small molecule therapies, granted Roche (SIX:ROG; OTCQX:RHHBY) options to license programs against unspecified targets for $190 million up front in April (see “RNA, Meet Small Molecules” “Arrakis Taps Roche as First Pharma Partner”)...