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
- 来源:
- 关键词:AlkenesBiologicalBiomedical ResearchCOVID-19 vaccinationCOVID-19 vaccineCarbonCellsChemicalsChemistryCollaborationsCollectionCommunicable DiseasesComparative StudyComplexDisciplineDiseaseDrug Delivery SystemsDrug FormulationsElementsEncapsulatedEndosomesFormulationFutureGenetic VectorsGoalsHealthHigh Pressure Liquid ChromatographyHumanHydrophobicityIndustrializationLaboratoriesLengthLifeLipidsLiposomesMammalian CellMeasurementMeasuresMembraneMembrane FluidityMessenger RNAMethodsMissionMolecular ConformationNucleic AcidsOligonucleotidesPhase TransitionPlasmidsPlayPositioning AttributePropertyPublic HealthRNARNA deliveryReporterResearchResourcesRoentgen RaysRoleSiliconSmall Interfering RNAStructureSystemTechniquesTechnologyTherapeuticTherapeutic EffectToxic effectTransfectionTransition TemperatureTransmission Electron MicroscopyUnited States National Institutes of HealthUnsaturated FatsVaccine TherapyWorkanaloganti-viral efficacybiophysical propertiescis trans isomerizationcytotoxicitydelivery vehicledesigndisabilitydisorder preventioneconomic impactexperimental studyfightingfluidityimprovedin vivoinnovationlipid nanoparticlelipophilicitymRNA deliverynanoparticlenoveloxidative damagepandemic preparednesspi bondpublic health relevanceresponsesuccesstherapeutic RNAuptakevaccine deliveryvectorviral RNAweaponszeta potential
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
期刊论文数量(0)
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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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