Pharmacokinetics and Pharmacodynamics of Bioengineered miR‐34a Prodrug

• DOI: 10.1096/fasebj.30.1_supplement.712.3
• Publication Date: 2023-11-26T16:48:44Z
• Authors: Pui Yan Ho; Wei‐Peng Wang; Qiu‐Xia Chen; Balasubrahmanyam ...; Patrick A. Limbach; Mei‐Mei Li; Joseph Lionel Jilek; Jing‐Xin Qiu; Hong‐Jian Zhang; Tianhong Li; Theodore Wun; Ralph DeVere White; Kit S Lam; Ai‐Ming Yu

The complexity of cancer has been demonstrated to closely align with an alteration in gene expression profiles. Dysregulated miRNAs control many fundamental biological processes including tumor progression through the suppression multiple target genes, suggesting development miRNA based therapy. Recently we have developed a novel approach biosynthesize chimeric tRNA/mir‐34a agents Escherichia coli on large scale, which may act as prodrug for miR‐34a replacement In this study, aimed define pharmacokinetics and pharmacodynamics bioengineered prodrug. We found that is susceptible Dicer other RNases (e.g., RNase A Angiogenin), yet protected from degradation when formulated vivo ‐jetPEI. Higher levels accumulation were seen mouse liver lung ‐jetPEI administered intravenously. further monitored metabolic fate human carcinoma cells deep sequencing qPCR analyses, our data precise production mature As result, caused significant downregulation genes CDK6, MET, SIRT1) sharp reduction growth A549 xenograft models. addition, examined acute effects biologic by analyzing blood chemistry profiles IL‐6 models, showed no signs toxicity. Therefore, illustrate fate, efficacy safety recombinant would exemplify promise research development.