Dynamic carriers for therapeutic RNA delivery

• 成果类型: Article
• 署名作者: Berger, Simone; Laechelt, Ulrich; Wagner, Ernst
• 署名单位: University of Munich; University of Munich; University of Vienna
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13723
• DOI: 10.1073/pnas.2307799120
• 发表日期: 2024-03-12
• 关键词: sirna-lipid nanoparticles; messenger-rna; in-vivo; gene delivery; systemic delivery; highly efficient; plasmid dna; pdna; polyplexes; release

摘要

Carriers for RNA delivery must be dynamic, first stabilizing and protecting therapeutic RNA during delivery to the target tissue and across cellular membrane barriers and then releasing the cargo in bioactive form. The chemical space of carriers ranges from small cationic lipids applied in lipoplexes and lipid nanoparticles, over medium- sized sequence- defined xenopeptides, to macromolecular poly-cations applied in polyplexes and polymer micelles. This perspective highlights the discovery of distinct virus- inspired dynamic processes that capitalize on mutual nanoparticle- host interactions to achieve potent RNA delivery. From the host side, subtle alterations of pH, ion concentration, redox potential, presence of specific proteins, receptors, or enzymes are cues, which must be recognized by the RNA nanocarrier via dynamic chemical designs including cleavable bonds, alterable physicochemical properties, and supramolecular assembly-disassembly processes to respond to changing biological microenvironment during delivery.