Explore recent mRNA, saRNA, circular RNA, and LNP research on delivery, therapeutic translation, safety, analytical characterization, and manufacturing.
Selected for substantive contributions to delivery, translation, analytics, manufacturing, and safety. Original publication dates and evidence levels are retained. This library covers the latest 120 days; individual published guides remain available.
Nine bile-acid-derived sterols varied hydroxylation and alkyl-tail chemistry to probe LNP organization and organ expression. Molecular simulations and experiments linked membrane descriptors with encapsulation and formulation behavior. Replacing cholesterol shifted expression toward the spleen, and a lead sterol enhanced antigen-specific responses. The work offers a preclinical formulation framework rather than validated prediction of human biodistribution.
Why it is included: Highlights sterols as an independent delivery-design axis; simulation correlations and acute animal tolerability do not establish long-term clinical safety.
James Collin Hickey; Tracoyia Roach; Britteny Cassaidy; Rudolf Hergesheimer; Noah Franklin; Jeffrey Morin; Sarah Wagman; Justin Cohen; David Morrissey; Javier Chaparro-Riggers; Patrick Lim Soo Molecular Pharmaceutics · DOI 10.1021/acs.molpharmaceut.6c00239
Bispecific antibodies were used to bridge PEG motifs on LNPs and selected cellular surface markers without elaborate chemical conjugation. The platform enabled targeted mRNA delivery in cell models and transferrin-receptor-associated delivery in vivo. Researchers also measured endosomal responses at different antibody-loading ratios. Splenic enrichment supports further immune-cell targeting studies, but does not establish a clinical delivery solution.
Why it is included: Provides a modular targeting workflow for immune-cell delivery studies; receptor expression, antibody loading, and in vivo translation remain critical limitations.
Yunhe Su; Joseph Choy; Xiang Liu; Yining Zhu; Jinghan Lin; Christine Wei; Kailei D. Goodier; Di Yu; Leonardo Cheng; Milan Patel; Xiaoya Lu; Jingyao Ma; Jialiang Wang; Hai-Quan Mao ACS Applied Materials & Interfaces · DOI 10.1021/acsami.6c06888
Acid-cleavable cholesterol-derived crosslinkers and PEG-diamines stabilized anionic LNPs that otherwise lost activity during purification. By tuning crosslinking architecture, researchers balanced structural integrity with RNA release and improved splenic mRNA expression. Mechanistic analyses implicated intracellular processing as well as release behavior. These formulation-specific animal results do not establish general T-cell targeting or clinical manufacturing readiness.
Why it is included: Expands accessible anionic formulation space for spleen delivery; crosslinker clearance, repeat dosing, and manufacturing comparability still need evaluation.
Seo‐Hyeon Bae; Jisun Lee; Jae‐Hun Ahn; Hosam Choi; Huijeong Choi; Jungmin Kim; Minho Kang; Ho Rim Oh; So Hyun Park; Eun Young Oh; Sanghyuk Jeon; Yeeun Lee; Yu‐Sun Lee; Na‐Young Lee; Hee‐Jin Bae; Jina Kwak; Jooil Kim; Nakyung Lee; Beomsun Kang; Ji‐Hye Kim; Eunsaem Song; Daesub Song; Hyunho Yoon; Sang‐Myeong Lee; Hyewon Youn; Kiyoun Lee; Byeong‐Cheol Kang; Jae‐Hwan Nam Advanced Science · DOI 10.1002/advs.76539
A library of 56 ionizable lipids combined biodegradable disulfide linkages with different hydrophobic tail lengths and branching patterns. Structure-activity testing linked tail architecture to endosomal escape, translation, and biocompatibility. Optimized particles reduced cytotoxicity and cytokine induction, with immune-response evaluation extending to a nonhuman primate model. These findings support lipid design, rather than establishing human safety.
Why it is included: Offers experimentally grounded tail-chemistry design rules and primate evidence; reduced inflammatory readouts do not guarantee clinical safety.
Zhuxiao Gu; Xinhong Xiong; Xiang Chen; Hanwen Zhang; Ning Gu; Lulu Xue Angewandte Chemie International Edition · DOI 10.1002/anie.6080664
Starting with a liver-tropic lead from 90 degradable lipidoids, researchers attached small-molecule ligands to redirect delivery toward the lung. The modified particles showed increased vitronectin association and enhanced pulmonary mRNA expression, with genome-editing proof of concept. This modular chemical approach retains the parent scaffold, but its targeting performance remains demonstrated in preclinical experimental conditions.
Why it is included: Shows how modest scaffold modification can alter protein-corona interactions and organ targeting; cross-species reproducibility and human selectivity require testing.
