1d ago
UC Davis advances bacterial-made microRNA therapy with renewed NCI funding
University of California, Davis has received a USD 1.18 million National Cancer Institute R01 renewal to advance a bioengineered microRNA therapeutic platform for non-small cell lung cancer (NSCLC), extending support for a program that produces therapeutic microRNAs through bacterial fermentation rather than chemical synthesis. The program is now in its eighth year of NCI support.
The award funds preclinical work by principal investigator Aiming Yu on a patented platform that produces microRNA (miRNA) agents through bacterial fermentation rather than chemical synthesis. The resulting bioengineered RNA molecules, which the lab terms BioRNAs, carry only naturally occurring modifications — in contrast to chemically synthesized miRNA mimics that incorporate extensive artificial modifications. Preliminary studies reported by the group found BioRNA-encoded miR-124-3p suppressed target gene expression and NSCLC cell viability more effectively than a commercially available chemically synthesized miRNA mimic. Two lead candidates, miR-124-3p and miR-22-3p, have demonstrated antiproliferative activity across multiple NSCLC cell lines in preclinical models; lipopolyplex-formulated monotherapy with each reduced tumor progression in animal models without reported hepatic, renal, or severe immunogenic effects, the team said.
The funded work will pursue three aims: characterizing the molecular similarities and differences between BioRNA and chemically synthesized miRNA mimics; defining how the lead BioRNAs regulate NSCLC metabolism and immune checkpoint protein expression, including programmed death-ligand 1 (PD-L1); and evaluating whether BioRNAs can improve outcomes of co-administered agents such as pemetrexed and platinum-based drugs in vivo.
While RNA therapeutics have reached the clinic through siRNA and antisense modalities, miRNA therapeutics have progressed more slowly because of delivery and stability challenges. UC Davis's BioRNA platform seeks to address part of that challenge by producing RNA molecules with naturally occurring modifications rather than chemically synthesized mimics. The approach remains preclinical, and no BioRNA-derived therapy has entered human trials.
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Summary
University of California, Davis has received a USD 1.18 million National Cancer Institute R01 renewal to advance bioengineered microRNA therapeutics for...