Center for Fetal Money Gene Transfer for HLB Diseases

Project: Research project

Description

DESCRIPTION (provided by applicant):
The intent of this proposal is to establish a Center for Fetal Monkey Gene
Transfer for Heart, Lung, and Blood Diseases. The immediate goal of this
Center is to explore critical issues for in utero gene transfer in the rhesus
monkey model, which closely simulates humans. We propose that performing gene
transfer prenatally will provide the best opportunity for eliminating the
pathology associated with many life-threatening congenital conditions because
delivery of a corrective gene early is likely to prevent damage in organs or
cells inaccessible later in life. However, before considering application for
human fetuses, it is essential that issues such as cell tropism, levels and
duration of gene expression, and safety be addressed in relevant animal models
such as the monkey. Our first Objective is to investigate the efficiency of
recombinant viral vector systems in transferring genes into fetal rhesus
monkeys in vivo for cardiac, pulmonary, and hematopoietic disorders. In
Objective 1, Specific Aim 1, we will explore the efficiency of transduction of
two integrating viral vector systems, self-inactivating HIV-1-derived
lentivirus and adeno-associated virus (AAV), using systemic and organ-targeting
approaches. In these studies, constitutive and cell-specific
promoters will be used, and we will transfer viral vector constructs into
fetal monkeys at defined gestational ages and based on developmental
milestones. In Specific Aim 2 of this Objective, we will determine whether
immune responses are generated to transgene products and/or vectors, and
confirm that organ structure and postnatal function is not altered as a result
of our prenatal interventions. Our second Objective focuses on providing
specialized services to NHLBI-funded investigators for fetal gene transfer for
heart, lung, or blood diseases. In Objective 2, Specific Aim 1, we will
provide our unique primate expertise, services, and resources to NHLBI-funded
investigators who wish to evaluate their viral and non-viral gene transfer
strategies in monkeys. In order to effectively provide these services,
Specific Aim 2 of this Objective includes a plan for administrative/scientific
oversight, a Scientific Advisory Committee, and outreach efforts for NHLBI-funded
investigators. We propose that by establishing the Center for Fetal
Monkey Gene Transfer for Heart, Lung, and Blood Diseases we will be able to
explore the efficiency of gene transfer strategies as they emerge, fully
investigate the potential effects of gene transfer on the fetus, infant, and
mother, and significantly advance the field of gene therapy for future human
application.
StatusFinished
Effective start/end date9/30/018/31/07

Funding

  • National Institutes of Health: $969,939.00
  • National Institutes of Health: $59,650.00
  • National Institutes of Health: $59,650.00
  • National Institutes of Health: $715,795.00
  • National Institutes of Health: $529,898.00
  • National Institutes of Health: $562,169.00
  • National Institutes of Health: $596,406.00

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Haplorhini
Genes
National Heart, Lung, and Blood Institute (U.S.)
Hematologic Diseases
Lung Diseases
Fetus
Heart Diseases
Dependovirus
Primates
Tropism
Genetic Therapy
Advisory Committees
Transgenes
Gestational Age
HIV-1
Safety
Research Personnel
Gene Expression
Lung
Transplants

ASJC

  • Medicine(all)