Postnatal and Prenatal Therapeutic Base Editing for Metabolic Diseases

代谢性疾病的产后和产前治疗碱基编辑

基本信息

  • 批准号:
    10668614
  • 负责人:
  • 金额:
    $ 641.57万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-08-01 至 2028-07-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY The potential for the development of novel therapeutic modalities has energized the genome editing field since it first emerged in the 1990s and especially since the demonstration of programmable genome editing with CRISPR-Cas9 by multiple groups in 2012. There has been substantial progress with ex vivo therapeutic applications of genome editing in patients in the past few years, most notably with CAR-T immunotherapies for cancer and with durable treatment of hemoglobinopathies. Progress with in vivo therapeutic applications, i.e., somatic cell genome editing, has been slower due to the technical challenges inherent in the delivery of genome- editing tools into the body. As of the time of this writing, there are few published examples of successful genome editing performed in vivo in primates (including humans), with almost all examples involving somatic genome editing in the liver: TTR with Cas9 nuclease delivered by lipid nanoparticles (LNPs), PCSK9 and ANGPTL3 with adenine base editors delivered by LNPs, and PCSK9 with meganucleases delivered by adeno-associated virus (AAV) vectors. The prospects for genome-editing therapies extend to before birth, with in utero genome editing having the potential to treat genetic diseases that result in significant morbidity and mortality before or shortly after birth. Although restricted to small animal models so far, in utero genome editing has proven effective in the liver, lungs, heart, and other organs. Our Overall Program seeks to build on these early successes, pursuing goals that that would be of major impact in advancing the field of therapeutic genome editing. Our three Research Projects seek to develop base-editing therapies targeting the liver in order to treat three rare metabolic genetic diseases: phenylketonuria (PKU), hereditary tyrosinemia type 1 (HT1), and mucopolysaccharidosis type 1 (MPSI). Lead Project 1 will focus on LNP-based postnatal treatment of PKU, with the aim to file an IND application by the end of the five-year funding period and begin a phase 1/2 clinical trial soon afterwards. Project 2 will focus on LNP-based postnatal treatment of HT1, with the aim to file an IND application and begin a clinical trial, and prenatal treatment of HT1, with the aim of performing preclinical studies during the five-year funding period to enable an eventual IND application if the postnatal clinical trial proves successful. Project 3 will focus on AAV-based postnatal and prenatal treatment of MPSI, with similar aims as Project 2. Unique, specialized Resource Cores focused on off-target editing and in utero treatment of small and large animals will be indispensable in achieving these aims.
项目总结

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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Kiran Musunuru其他文献

Kiran Musunuru的其他文献

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{{ truncateString('Kiran Musunuru', 18)}}的其他基金

ADMINISTRATIVE CORE
行政核心
  • 批准号:
    10668615
  • 财政年份:
    2023
  • 资助金额:
    $ 641.57万
  • 项目类别:
LEAD PROJECT 1: PHENYLKETONURIA (PKU)
牵头项目 1:苯丙酮尿症 (PKU)
  • 批准号:
    10668618
  • 财政年份:
    2023
  • 资助金额:
    $ 641.57万
  • 项目类别:
Diagnosis, Prevention, And Treatment Of Cardiovascular Diseases With Genome Editing
利用基因组编辑诊断、预防和治疗心血管疾病
  • 批准号:
    10339415
  • 财政年份:
    2019
  • 资助金额:
    $ 641.57万
  • 项目类别:
Diagnosis, Prevention, And Treatment Of Cardiovascular Diseases With Genome Editing
利用基因组编辑诊断、预防和治疗心血管疾病
  • 批准号:
    10112299
  • 财政年份:
    2019
  • 资助金额:
    $ 641.57万
  • 项目类别:
Diagnosis, Prevention, And Treatment Of Cardiovascular Diseases With Genome Editing
利用基因组编辑诊断、预防和治疗心血管疾病
  • 批准号:
    9896848
  • 财政年份:
    2019
  • 资助金额:
    $ 641.57万
  • 项目类别:
Diagnosis, Prevention, And Treatment Of Cardiovascular Diseases With Genome Editing
利用基因组编辑诊断、预防和治疗心血管疾病
  • 批准号:
    10561719
  • 财政年份:
    2019
  • 资助金额:
    $ 641.57万
  • 项目类别:
Permanent alteration of PCSK9 in vivo genome editing
PCSK9 体内基因组编辑的永久改变
  • 批准号:
    9307483
  • 财政年份:
    2017
  • 资助金额:
    $ 641.57万
  • 项目类别:
High-throughput screening and stem cell modeling of causal eQTL variants
因果 eQTL 变异的高通量筛选和干细胞建模
  • 批准号:
    9242768
  • 财政年份:
    2016
  • 资助金额:
    $ 641.57万
  • 项目类别:
Stem Cells Models of Familial Combined Hypolipidemia
家族性混合性低脂血症的干细胞模型
  • 批准号:
    9198670
  • 财政年份:
    2016
  • 资助金额:
    $ 641.57万
  • 项目类别:
Stem Cells Models of Familial Combined Hypolipidemia
家族性混合性低脂血症的干细胞模型
  • 批准号:
    9212742
  • 财政年份:
    2016
  • 资助金额:
    $ 641.57万
  • 项目类别:

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