Authors
Xucheng Hou, Changyue Yu, Yonger Xue, Yuwei Liu, Diana D Kang, Jeffrey L Bennett, Eliza Bliss-Moreau, Mi Ni, Yujie Liu, Gang Fang, Ya Ying Zheng, Siyu Wang, Meng Tian, Yichen Zhong, Haoyuan Li, Zhengwei Liu, Dinglingge Cao, Yizhou Dong
Published in
Bioactive materials. Volume 68. Pages 231-240. Epub Sep 03, 2026.
Abstract
The therapeutic potential of oligonucleotides (oligos) is limited by insufficient delivery to extrahepatic tissues. In vitro assays often fail to accurately predict in vivo behavior, while testing each oligo candidate in animals remains inherently low throughput. Here, we conceive a barcoded oligonucleotide system (BOLT), a platform that enables high-throughput in vivo evaluations of small-molecule ligands and identifies tissue-specific oligo delivery. BOLT integrates rational design of oligo barcodes, modular conjugation chemistry, and next-generation sequencing (NGS)-based quantification, allowing simultaneous evaluation of many chemically diverse ligand-oligo conjugates within a single animal. Notably, this platform is applicable in both mice and nonhuman primates (NHPs). Using BOLT, we discovered ligands with tropism for tissues such as the brain, lung, and muscle. Collectively, these results indicate that the BOLT platform can accelerate the discovery of tissue-targeting ligands for broad oligo therapeutics.
PMID:
42733790
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.
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