Using Cardiac Targeting Peptide to deliver miRNA for molecular reversal of heart failure

使用心脏靶向肽传递 miRNA 以分子逆转心力衰竭

基本信息

  • 批准号:
    10481720
  • 负责人:
  • 金额:
    $ 28.47万
  • 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:
    2022-07-13 至 2024-07-12
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY/ABSTRACT Heart failure (HF) is a common disease with well-documented morbidity and mortality that affects approximately 23 million people globally, including 6 million in the US. Current HF medications such as Angiotensin Converting Enzyme (ACE) Inhibitors or Angiotensin Receptor Blockers (ARBs) treat the symptoms of HF versus the root cause of the disease, which includes stressed myocardium that leads to hypertrophic cardiomyocytes and endothelial inflammation. CaMKIIδ is a signaling molecule that regulates cellular pathways involved in excitation‑contraction coupling and relaxation events in the heart and transcriptional activation of genes related to cardiac hypertrophy, inflammation, and arrhythmias. If left uncorrected, CaMKIIδ‑regulated changes culminate in a dysfunctional myocardium and HF. The goal of this STTR Phase I project is to address this root cause of HF by delivering miRNA to cardiomyocytes to down-regulate the over-expression and/or activation of CaMKIIδ because this may allow damaged cardiomyocytes to regain normal function. To achieve this goal, a specific miRNA will be selected that effectively inhibits the expression of CaMKIIδ in vivo. This miRNA will then be conjugated to the proprietary cell penetrating peptide, Cardiac Targeting Peptide (CTP), developed by Vivasc Therapeutics. This will create a CTP-miRNA conjugate that will deliver this nucleotide specifically and directly to cardiomyocytes. CTP is a novel, synthetic peptide that has transduced (i) normal mouse hearts in vivo (peak uptake at 15 minutes after injection), (ii) explanted human heart tissue, and (iii) human derived iPSC beating cardiomyocytes. CTP has demonstrated robust transduction of normal cardiomyocytes while sparing myofibroblasts, endothelial cells, and fibroblasts present in scar tissue. To date, CTP conjugates have transduced cardiomyocytes carrying intact cargoes as diverse as radioisotopes, nucleic acids, other peptides, and conjugates as large as the biotin-streptavidin complex. The team’s preliminary data has shown that CTP is fully capable of carrying miRNA in a similar manner. The hypothesis is that CTP-miRNA will deliver miRNA to cardiomyocytes that are over expressing CaMKIIδ, thereby allowing damaged cardiomyocytes to regain normal function. The aims are: 1) deliver specific miRNAs to the hearts of HF mouse models to demonstrate their efficacy in reversing HF physiology and 2) test the in vivo biodistribution of CTP-miRNA using a dual-labeled CTP-miRNA. Phase II plans include conducting studies of optimized CTP-miRNA in larger animal models of HF and IND- enabling studies to support an Investigational New Drug (IND) submission for approval of a Phase 1 clinical trial. Upon approval, this treatment could potentially be prescribed to HF patients with cardiac hypertrophy, inflammation, and arrhythmias.
项目总结/文摘

项目成果

期刊论文数量(0)
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G IAN GALLICANO其他文献

G IAN GALLICANO的其他文献

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{{ truncateString('G IAN GALLICANO', 18)}}的其他基金

Investigating deskmoplakin during vasculogenesis
研究血管生成过程中的 deskmoplakin
  • 批准号:
    6574003
  • 财政年份:
    2002
  • 资助金额:
    $ 28.47万
  • 项目类别:
Investigating deskmoplakin during vasculogenesis
研究血管生成过程中的 deskmoplakin
  • 批准号:
    6685992
  • 财政年份:
    2002
  • 资助金额:
    $ 28.47万
  • 项目类别:
Investigating deskmoplakin during vasculogenesis
研究血管生成过程中的 deskmoplakin
  • 批准号:
    6818777
  • 财政年份:
    2002
  • 资助金额:
    $ 28.47万
  • 项目类别:
Investigating deskmoplakin during vasculogenesis
研究血管生成过程中的 deskmoplakin
  • 批准号:
    6989775
  • 财政年份:
    2002
  • 资助金额:
    $ 28.47万
  • 项目类别:
FUNCTIONAL ANALYSIS: BAND 6 DURING MAMMALIAN DEVELOPMENT
功能分析:哺乳动物发育过程中的带 6
  • 批准号:
    2816005
  • 财政年份:
    1998
  • 资助金额:
    $ 28.47万
  • 项目类别:
FUNCTIONAL ANALYSIS: BAND 6 DURING MAMMALIAN DEVELOPMENT
功能分析:哺乳动物发育过程中的带 6
  • 批准号:
    2024970
  • 财政年份:
    1997
  • 资助金额:
    $ 28.47万
  • 项目类别:
Animal Models Core
动物模型核心
  • 批准号:
    7933855
  • 财政年份:
  • 资助金额:
    $ 28.47万
  • 项目类别:
Animal Models Core
动物模型核心
  • 批准号:
    8134873
  • 财政年份:
  • 资助金额:
    $ 28.47万
  • 项目类别:
Animal Models Core
动物模型核心
  • 批准号:
    8379857
  • 财政年份:
  • 资助金额:
    $ 28.47万
  • 项目类别:

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