Developing Gene Editing Therapeutics, Biodegradable Polymeric Delivery Vehicles, and High-throughput Platforms for the Treatment of Cystic Fibrosis
开发用于治疗囊性纤维化的基因编辑疗法、可生物降解的聚合物递送载体和高通量平台
基本信息
- 批准号:10301702
- 负责人:
- 金额:$ 10.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:3-DimensionalAminesBase PairingBiocompatible MaterialsBiodistributionBiologicalBiologyBiomedical EngineeringBlood CirculationCRISPR/Cas technologyCell LineCellsChemicalsChloridesClinical TrialsCommunitiesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDNADNA RepairDevelopmentDevelopment PlansDiagnosisDiseaseDisease modelDoctor of PhilosophyDrug Delivery SystemsEncapsulatedEngineeringEstersFamilyGenesGeneticGenetic DiseasesGoalsGuide RNAHalf-LifeHealthHereditary DiseaseImpairmentIn VitroInterdisciplinary StudyKnowledgeLibrariesLungLung diseasesLung infectionsMentorsMethodsModelingMutationNanotechnologyNonsense CodonOligonucleotidesOrganoidsOther GeneticsPatientsPeptide Nucleic AcidsPhysiologicalPhysiologyPolymer ChemistryPolymersPostdoctoral FellowProteinsPublic HealthRNA-Directed DNA PolymeraseReagentRegulator GenesReporterResearchResearch PersonnelSafetyScientistScreening procedureSiteStructure-Activity RelationshipSystemTechnologyTestingTherapeuticTherapeutic AgentsTissue EngineeringTissuesTrainingTranslationsTreatment EfficacyUnited StatesUniversitiesWorkbasebiodegradable polymerburden of illnesscareercareer developmentcell typeclinical translationclinically relevantcurative treatmentscystic fibrosis patientsdesigndesign and constructiondisease-causing mutationendonucleaseengineered nucleasesexperienceexperimental studygenome editinghigh throughput screeninghigh throughput technologyimprovedin vitro Modelin vivoinnovationnanomedicinenanoparticlenovelnucleasenucleic acid deliverynucleic acid-based therapeuticsresponsescreeningskillstherapeutic developmenttherapeutic genome editingthree dimensional cell culturethree-dimensional modelingtooluptake
项目摘要
Project Summary
Cystic fibrosis (CF) is a progressive genetic disorder caused by mutations in the CF transmembrane
conductance regulator (CFTR) gene. Premature stop codon mutations including W1282X are among the most
severe and there are no curative treatments for patients. Genome editing agents could offer promising
therapeutics applicable to all CF patients. Engineered nucleases including CRISPR/Cas9 systems that can
catalyze correction of disease-causing mutation(s) have shown promise and entered clinical trials. To mitigate
aberrant nuclease activity and reduce off-target effects, prime editing technology combines a catalytically
impaired Cas9 endonuclease fused with an engineered reverse transcriptase programmed with a prime editing
guide RNA (pegRNA) that also encodes the desired edit. As an alternative technology, triplex-forming peptide
nucleic acids (PNAs) have no intrinsic nuclease activity and stimulate endogenous DNA repair with low off-target
effects when bound adjacent to the target site and co-delivered with donor DNA oligonucleotides. Despite
advances in gene editing technology, in vivo delivery remains a primary barrier to clinical translation. The goal
of the proposed research is to develop a genome editing-based therapeutic strategy for treating the
W1282X nonsense CF mutation as well as high-throughput technologies for identifying effective vehicles
for in vivo therapeutic nucleic acid delivery. In Aim 1, PNA- and CRISPR/Cas9 prime editing-based gene
editing reagents will be designed to correct the W1282X mutation, encapsulated into poly(amine-co-ester)
(PACE) nanoparticles (NPs), and tested in vitro and in vivo. In Aim 2, novel PACE materials will be developed
for in vivo delivery of nucleic acid-based therapeutics to the lungs and assessed using high-throughput in vivo
platforms to determine the structure-function relationships guiding physiological fate. In Aim 3, physiologically
relevant 3D culture models will be developed as high-throughput screening tools to assess delivery and efficacy
of CF therapies. Overall, the proposed interdisciplinary research is highly clinically relevant, furthering the
translation of promising gene editing/nucleic acid therapeutics for CF and other genetic diseases.
Dr. Piotrowski-Daspit received her Ph.D. in Chemical and Biological Engineering and is currently a
postdoctoral fellow in the Department of Biomedical Engineering at Yale University. Thus far, she has been
developing polymeric NPs for nucleic acid delivery and high-throughput in vivo tools. The career development
plan outlines a comprehensive strategy for acquiring the technical, conceptual, and professional skills required
to complete the proposed studies and launch an independent research career. The proposed training would
enable her to gain significant experience in therapeutic development for CF and integrate her into the CF
research community. The training plan, together with her background in biomedical engineering, biomaterials
and drug delivery, will place her among a select group of scientists with the skills and breadth of knowledge
necessary to effectively pursue interdisciplinary work on nucleic acid delivery and editing of genetic disorders.
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Alexandra Sarah Annukka Piotrowski-Daspit其他文献
Alexandra Sarah Annukka Piotrowski-Daspit的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Alexandra Sarah Annukka Piotrowski-Daspit', 18)}}的其他基金
Developing Gene Editing Therapeutics, Biodegradable Polymeric Delivery Vehicles, and High-throughput Platforms for the Treatment of Cystic Fibrosis
开发用于治疗囊性纤维化的基因编辑疗法、可生物降解的聚合物递送载体和高通量平台
- 批准号:
10836095 - 财政年份:2023
- 资助金额:
$ 10.98万 - 项目类别:
Developing Gene Editing Therapeutics, Biodegradable Polymeric Delivery Vehicles, and High-throughput Platforms for the Treatment of Cystic Fibrosis
开发用于治疗囊性纤维化的基因编辑疗法、可生物降解的聚合物递送载体和高通量平台
- 批准号:
10477028 - 财政年份:2021
- 资助金额:
$ 10.98万 - 项目类别:
Developing Gene Editing Therapeutics, Biodegradable Polymeric Delivery Vehicles, and High-throughput Platforms for the Treatment of Cystic Fibrosis
开发用于治疗囊性纤维化的基因编辑疗法、可生物降解的聚合物递送载体和高通量平台
- 批准号:
10703623 - 财政年份:2021
- 资助金额:
$ 10.98万 - 项目类别:
相似海外基金
More sustainable biocatalytic imine reductions to chiral amines with hydrogen-driven NADPH recycling operated in batch and continuous flow
通过批量和连续流操作的氢驱动 NADPH 回收,更可持续地生物催化亚胺还原为手性胺
- 批准号:
2889869 - 财政年份:2023
- 资助金额:
$ 10.98万 - 项目类别:
Studentship
Organoborane-catalysed approaches to biologically active amines
有机硼烷催化制备生物活性胺的方法
- 批准号:
EP/Y00146X/1 - 财政年份:2023
- 资助金额:
$ 10.98万 - 项目类别:
Research Grant
Transforming Amines into Complex Polycyclic Molecules and Bioactive Natural Products
将胺转化为复杂的多环分子和生物活性天然产物
- 批准号:
2247651 - 财政年份:2023
- 资助金额:
$ 10.98万 - 项目类别:
Standard Grant
Ti-catalyzed cascading hydroaminoalkylation as a route to complex functionalized amines
Ti 催化级联氢氨基烷基化作为制备复杂官能化胺的途径
- 批准号:
10750347 - 财政年份:2023
- 资助金额:
$ 10.98万 - 项目类别:
New Photocatalytic C-C Bond-Forming Reactivity of Unprotected Primary Amines
未受保护伯胺的新光催化 C-C 键形成反应
- 批准号:
EP/X026566/1 - 财政年份:2023
- 资助金额:
$ 10.98万 - 项目类别:
Research Grant
Nickel Cross-Coupling Cascades with α-Heteroatom Radicals to Prepare Sterically Hindered Alcohols and Amines
镍与α-杂原子自由基交叉偶联级联制备位阻醇和胺
- 批准号:
10604535 - 财政年份:2023
- 资助金额:
$ 10.98万 - 项目类别:
Towards a better understanding of the effect of the pentafluorosulfanyl group on the lipophilicity and acid/base properties of alcohols and amines
更好地了解五氟硫基对醇和胺的亲脂性和酸/碱性质的影响
- 批准号:
571856-2021 - 财政年份:2022
- 资助金额:
$ 10.98万 - 项目类别:
Alliance Grants
Development of Strategies for the Enantioselective Synthesis of Heterocycles and Acyclic Amines
杂环和无环胺对映选择性合成策略的发展
- 批准号:
10656344 - 财政年份:2022
- 资助金额:
$ 10.98万 - 项目类别:
Pd-Catalyzed C(sp3)-H Functionalizations Directed by Free Alcohols and Boc-Protected Amines
由游离醇和 Boc 保护的胺引导的 Pd 催化 C(sp3)-H 官能化
- 批准号:
10606508 - 财政年份:2022
- 资助金额:
$ 10.98万 - 项目类别:














{{item.name}}会员




