Precision microRNA medicine in cancer
癌症中的精准 microRNA 医学
基本信息
- 批准号:10227099
- 负责人:
- 金额:$ 105万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-08-22 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:3&apos Untranslated RegionsAffectAgingAllelesAmericanAnimal ModelAreaBiological AssayCancer PatientCell CycleCell LineCell ProliferationCellsChargeClinicClinicalClinical InvestigatorClinical Trials UnitCommunitiesCoupledDevelopmentDiagnosticDiseaseEyeFutureGenomeGoalsHumanImmune TargetingIndividualInstitutesMalignant NeoplasmsMedicineMetabolismMethodsMicroRNAsNeoplasm MetastasisNon-Small-Cell Lung CarcinomaOncogenesOrganoidsPathway interactionsPatientsPhase I Clinical TrialsPhysiciansProcessRNARegimenResearchResourcesRoleTestingTherapeuticTissuesTranscriptTranslatingTranslationsTumor TissueUntranslated RNAValidationVisionWorkXenograft ModelXenograft procedurebasecancer biomarkersclinical applicationdesignimmune checkpointmedical schoolsmiRNA expression profilingmouse modelnovelnovel strategiespersonalized medicinepersonalized therapeuticpre-clinicalprofiles in patientsprogramsscreeningstandard of caresuccesstargeted deliverytheranosticstherapeutic miRNAtherapeutic targettumor
项目摘要
MicroRNAs (miRNAs) are regulatory RNA molecules that control a large variety of cancer processes including
proliferation/cell cycle, survival, metabolism and metastasis, and have led the charge in the non-coding RNA
(ncRNA) revolution. My lab has shown that they regulate key cancer genes and that their mis-expression can
be both informational AND causal in cancer. This presents a unique diagnostic and therapeutic (theranostic)
opportunity to use miRNA-based strategies as effective cancer biomarkers AND therapeutics. My general
strategy is a unique three-pronged approach that grows and harnesses the new discoveries in miRNAs,
coupled with the expertise in mouse models and clinical capabilities at HIRM/BIDMC/DFHCC, including:
a. Comprehensive discovery and functional validation in the miRNA space in cancer. Even though the vast
majority of human transcripts are non-coding and the vast majority of disease associated SNP lie in the nc
portion of the genome, we understand very little of their roles in human cells. Here we will discover the key
miRNAs mis-expressed in human cancers and their microenvironment, and mine the miRNA and 3’UTR
portions of the genome for novel cancer alleles. These will be functionally validated in cell line assays, patient
derived organoid (PDO) and xenograft (PDX) animal models. b. Overcoming delivery barriers to cancer tissue
and target engagement. While we have had some success in targeting these novel RNA-based molecules to
cancer tissues, the current approaches are largely non-tissue specific and we propose a program to make this
more effective, testing intratumoral and ex vivo delivery and to ultimately personalize targeting. c. Advancing
miRNA-based medicine to the clinic. Here I propose to use the miRNA profiles of patient tumor tissue to guide
personalized treatment options based on patient miRNA deficiencies, targeting immune checkpoints etc., even
to design a personalized regimen of miRNA-based molecules for therapy, initially testing the idea in PDO and
PDX models. In addition, I propose to capitalize on my proximity to the best physicians and Phase I clinical
trials units to facilitate the translation of our preclinical work to clinical applications, in both diagnostic and
therapeutic areas. I hope these novel, individualized methods will converge on standard of care for cancer
patients in the future. While this approach could be relevant to many difficult-to-treat tumor types, I present my
rationale for starting in PDAC and NSCLC, where I have been successful in collaborating with clinical
investigators to apply our expertise here.
While miRNA therapeutics are still a novel approach to broadly target cancer pathways, we are the first to
propose miRNA screening with an eye towards personalized therapeutics and integrating miRNAs into
standard of care for cancer patients. As the Director of the new Harvard Medical School Institute for RNA
Medicine, I will pursue all of these goals as well as attempt to harness the resources (research /clinical
/intellectual) of the Harvard community in these efforts, and hope to deliver these advancements to patients.
MicroRNAs (miRNAs)是一种调控RNA分子,控制着多种癌症过程,包括
项目成果
期刊论文数量(0)
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{{ truncateString('FRANK J. SLACK', 18)}}的其他基金
Targeting microRNAs in the tumor microenvironment with pHLIP conjugated next generation chemically modified PNAs
使用 pHLIP 结合下一代化学修饰的 PNA 靶向肿瘤微环境中的 microRNA
- 批准号:
10548741 - 财政年份:2020
- 资助金额:
$ 105万 - 项目类别:
Targeting microRNAs in the tumor microenvironment with pHLIP conjugated next generation chemically modified PNAs
使用 pHLIP 结合下一代化学修饰的 PNA 靶向肿瘤微环境中的 microRNA
- 批准号:
10334460 - 财政年份:2020
- 资助金额:
$ 105万 - 项目类别:
Targeting microRNAs in the tumor microenvironment with pHLIP conjugated next generation chemically modified PNAs
使用 pHLIP 结合下一代化学修饰的 PNA 靶向肿瘤微环境中的 microRNA
- 批准号:
10089424 - 财政年份:2020
- 资助金额:
$ 105万 - 项目类别:
Juvenile microRNAs promoting healthier adult aging
青少年 microRNA 促进更健康的成年衰老
- 批准号:
9901417 - 财政年份:2018
- 资助金额:
$ 105万 - 项目类别:
Juvenile microRNAs promoting healthier adult aging
青少年 microRNA 促进更健康的成年衰老
- 批准号:
10388101 - 财政年份:2018
- 资助金额:
$ 105万 - 项目类别:
MicroRNAs to Understand Cause and Outcome in Breast Cancer
MicroRNA 用于了解乳腺癌的原因和结果
- 批准号:
8856516 - 财政年份:2014
- 资助金额:
$ 105万 - 项目类别:
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