Development of a Gectosome Therapy for Cardiovascular Diseases
心血管疾病的基因组疗法的开发
基本信息
- 批准号:10384422
- 负责人:
- 金额:$ 31.68万
- 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:2022-01-01 至 2023-12-31
- 项目状态:已结题
- 来源:
- 关键词:ANGPTL3 geneAddressAffectAllelesAntibody TherapyAntisense OligonucleotidesArterial Fatty StreakBiological ProductsBlood CirculationC57BL/6 MouseCardiovascular DiseasesCellsCholesterolClustered Regularly Interspaced Short Palindromic RepeatsColoradoComplexCoronaryCoronary ArteriosclerosisDevelopmentDiseaseDoseEncapsulatedEnzymesEvaluationEventFamilial HypercholesterolemiaFeasibility StudiesGene SilencingGenesGoalsGuide RNAHealthHepatocyteImmunityIndividualLaboratoriesLicensingLiverLow Density Lipoprotein ReceptorLow-Density LipoproteinsMediatingMedicalMethodsModalityMonoclonal AntibodiesMusMutationPatientsPersonsPhasePhase I Clinical TrialsProductionRNARNA InterferenceRare DiseasesRiskSafetySmall Business Technology Transfer ResearchSmall Interfering RNASpecificitySystemTechnologyTherapeuticTherapeutic AgentsTherapeutic EffectToxic effectTranslatingUncertaintyUniversitiesVesicleWorkbasecardiovascular disorder therapyclinical candidateclinical translationdrug developmentexperimental studyin vivoinnovationinnovative technologiesknock-downnovel therapeuticsrare genetic disorderresponseside effectsuccesstherapeutic targettranscriptome sequencingtreatment response
项目摘要
Project Summary
Vesicle Therapeutics Inc aims to develop and commercialize a new therapy for homozygous
familial hypercholesterolemia (hoFH). A majority of hoFH is caused by mutations in both alleles
of the gene encoding the LDL receptor (LDLR). Since the efficacy of both statins and PCSK9
antibody therapies largely depends on functional LDL receptors, patients with hoFH show limited
responses to these existing therapies. There is no cure for hoFH, and few options are available
to treat the diseases. Angiopoietin-like 3 (ANGPTL3) has emerged as a possible therapeutic
target for hoFH as individuals deficient in ANGPTL3 do not develop coronary atherosclerotic
plaque. The RNA targeting CRISPR enzyme LwaCas13 can turn off genes by RNA depletion
analogous to RNAi but with very lower rate of off-target gene silencing. The absence of safe
delivery methods currently limits the therapeutic potential of LwaCas13. The Liu laboratory at the
University of Colorado-Boulder developed an innovative intracellular biologics delivery system
called Gectosomes. The overall objective of this phase I STTR project is to demonstrate that
silencing of ANGPTL3 by gectosome delivery of LwaCas13a/ANGPTL3 crRNA is efficacious in
lowering LDL-C with acceptable safety profile in mice. The proposed strategy combines two
innovative technologies for potential clinical translation. The proposed studies are feasible based
on our previous success with gectosome delivery of CRISPR RNP that causes inactivation of
PCSK9 in mouse liver. ANGPTL3 is primarily expressed in hepatocytes and secreted into the
bloodstream. The liver is readily accessible by gectosomes. LwaCas13a-mediated RNA depletion
is reversible and may have fewer safety concerns than gene editing. We will determine the
efficacy and safety of ANGPTL3 suppression by LwaCas13a in mice and this work is necessary
for further studies to advance a potential therapeutic solution for a rare disease.
项目总结
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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XUEDONG LIU其他文献
XUEDONG LIU的其他文献
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{{ truncateString('XUEDONG LIU', 18)}}的其他基金
Neuron Specific mRNA Transfer With Fusogenic Microvesicles
使用融合微泡进行神经元特异性 mRNA 转移
- 批准号:
10578732 - 财政年份:2022
- 资助金额:
$ 31.68万 - 项目类别:
Programmable Microvesicles for Intracellular Macromolecule Delivery
用于细胞内大分子递送的可编程微泡
- 批准号:
10350387 - 财政年份:2022
- 资助金额:
$ 31.68万 - 项目类别:
Programmable Microvesicles for Intracellular Macromolecule Delivery
用于细胞内大分子递送的可编程微泡
- 批准号:
10544761 - 财政年份:2022
- 资助金额:
$ 31.68万 - 项目类别:
Programmable Microvesicles for Intracellular Macromolecule Delivery
用于细胞内大分子递送的可编程微泡
- 批准号:
10798752 - 财政年份:2022
- 资助金额:
$ 31.68万 - 项目类别:
Neuron Specific mRNA Transfer With Fusogenic Microvesicles
使用融合微泡进行神经元特异性 mRNA 转移
- 批准号:
10451377 - 财政年份:2022
- 资助金额:
$ 31.68万 - 项目类别:
Programmable Microvesicles for Intracellular Macromolecule Delivery
用于细胞内大分子递送的可编程微泡
- 批准号:
10676021 - 财政年份:2022
- 资助金额:
$ 31.68万 - 项目类别:
Quantitative Analysis of Mechanochemical Signaling in Wound Response
伤口反应中机械化学信号的定量分析
- 批准号:
9303654 - 财政年份:2016
- 资助金额:
$ 31.68万 - 项目类别:
Quantitative Analysis of Mechanochemical Signaling in Wound Response
伤口反应中机械化学信号的定量分析
- 批准号:
8913630 - 财政年份:2015
- 资助金额:
$ 31.68万 - 项目类别:
Quantitative Analysis of Mechanochemical Signaling in Wound Response
伤口反应中机械化学信号的定量分析
- 批准号:
9768888 - 财政年份:2015
- 资助金额:
$ 31.68万 - 项目类别:
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