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

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $73,558

## Abstract

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.

## Key facts

- **NIH application ID:** 10511399
- **Project number:** 1R03EB033487-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Annaliese Franz
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $73,558
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10511399

## Citation

> US National Institutes of Health, RePORTER application 10511399, Cationic Silyl-lipids for Enhanced Delivery of Anti-viral RNA Therapeutics (1R03EB033487-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10511399. Licensed CC0.

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