Cationic Silyl-lipids for Enhanced Delivery of Anti-viral RNA Therapeutics

用于增强抗病毒 RNA 治疗药物递送的阳离子甲硅烷基脂质

基本信息

  • 批准号:
    10685412
  • 负责人:
  • 金额:
    $ 7.65万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-09-01 至 2024-05-31
  • 项目状态:
    已结题

项目摘要

PROJECT ABSTRACT Liposomes, including nucleic acid complexed lipid nanoparticles (LNPs) have shown success in drug delivery and formulation of sensitive RNA-based therapeutics, including the recent example of the mRNA Sar-COV-2 vaccine. The goal of this proposal is to synthesize and evaluate novel silyl-containing lipid structures to access innovative cationic lipid structures representing new chemical space for biomedical research. Three classes of cationic silyl-lipids will be synthesized in modular fashion to access structural and conformational cationic lipid analogs that have implications in the phase transition temperature and the fluidity of the bilayer, influencing the stability, toxicity, and fusogenicity of silyl- LNPs. This proposal is organized into three specific aims: 1) Synthesis of novel silyl-containing lipids as diverse cationic lipid vectors using catalytic hydrosilylation methods, particularly focusing on the modular incorporation of a silyldimethyl group as a bioisostere of a cis carbon–carbon double bond of known unsaturated cationic lipid vectors, as well as other silyl groups with relevant properties to modulate the branching and chain length of the resulting lipid. Target molecules include silyl analogs of DOTMA, DOTAP and DOSPA. 2) Evaluate biophysical properties of liposome formation and silyl-LNP formulation through established characterization techniques including measurements of zeta potential, transmission electron microscopy and small-angle X-ray scattering. The RNA/silyl-LNP complex will be characterized using HPLC to quantify RNA encapsulation. 3) Perform in cellulo studies to provide a comparative study on transfection efficacy of siRNA and cytotoxicity of silyl-lipid LNPs with commercially available liposome RNA delivery systems. Overall, our studies aim to demonstrate the potential of cationic silyl-lipids as novel structures for LNP formulation with the long-term goal to develop novel delivery systems and improve transfection efficacy of anti-viral RNA therapeutics.
项目摘要

项目成果

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Annaliese Franz其他文献

Annaliese Franz的其他文献

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{{ truncateString('Annaliese Franz', 18)}}的其他基金

Cationic Silyl-lipids for Enhanced Delivery of Anti-viral RNA Therapeutics
用于增强抗病毒 RNA 治疗药物递送的阳离子甲硅烷基脂质
  • 批准号:
    10511399
  • 财政年份:
    2022
  • 资助金额:
    $ 7.65万
  • 项目类别:

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