PROJECT SUMMARY
The goal of this project is to develop
(NHP)
diseases
NHP
that
diseases
models
uncurable
of
two
female
require
in
The
in
already
staff
discovered
relevant
cutting-edge
aims:
public,
To
training
genetic
research
NHP
disease
a national resource for the preservation and use of non-human primate
models of human genetic diseases. Numerous laboratories are developing novel therapies for genetic
that require large animal models to assess safety and efficacy. Compared to rodents and other animals,
models of human diseases have been far more valuable for developing new drugs and other approaches
go on to be successfully used in humans. Recently, a variety of spontaneous NHP models of human genetic
have been identified at the U.S. National Primate Research Centers (NPRCs). These NHP genetic
present extraordinary opportunities to significantly advance the study and treatment of currently
diseases, including the pre-clinical testing of state-of-the-art precision medicine approaches.
constraints impact the efficient breeding and availability of these NHP models. First, since most
the identified diseases display autosomal recessive i nheritance, on average only 1 in 4 offspring produced by
allele carriers is homozygous and affected. There are often insufficient numbers of breeding age male and
allele carriers to produce sufficient subjects in a timely way. Second, for ultra-rare alleles, breeding may
the use of a l imited number of allele carriers located at multiple NPRC facilities. Third, r ecen increases
demand for NHPs for vaccine research severely threatens the long-term availability of model allele carriers.
overcome these challenges, we aim to generate a National NHP Model Embryo Resource (NNMER).
Oregon NPRC (ONPRC) will optimize and implement state-of-the-art protocols for NHP gamete collection,
vitro f ertilization, blastocyst genotyping and embryo cryopreservation of affected and carrier embryos of
characterized disease models. Moreover, the ONPRC wil provide training and support for veterinary
at five partnering NPRCs to ensure t he efficient collection of gametes from both current and newly
disease model carriers located at each center. The long-term goal is to provide a biomedically-
national resource, accessible to any investigator interested in NHP genetic models, that will enable
preclinical research and therapeutic development. To achieve these oals, we propose the following
(1) To establish a national NHP genetic disease model gamete, embryo and fibroblast resource and a
searchable tool for the long-term preservation of and accessibility to valuable NHP disease models;
support nationwide collection of NHP gametes and the generation of genotyped model embryos by providing
in state-of-the-art assisted reproductive technologies; and (3) To promote widespread use of the NHP
disease embryo resource through systematic outreach efforts aimed at reaching both clinicians and
investigators nationwide. This proposed highly novel resource will provide powerful, genetically parallel,
models to investigators and clinicians advancing studies to understand mechanisms of human genetic
pathogenesis and to evaluate new therapeutic strategies.
Several
t
To
l
g
(2)