Document text
Principal Investigator: Alan W. Flake
Organization: CHILDREN'S HOSP OF PHILADELPHIA
Fiscal Year: 2023
Award: $1,069,284
Funding agency: National Institute of Neurological Disorders and Stroke
PROJECT SUMMARY
Many monogenic diseases strike prior to or soon after birth and cause significant morbidity and mortality. In utero
genome editing (IUGE) takes advantage of normal fetal properties, including small size, abundant progenitor
cells, and immature immune system, to safely and efficiently institute the genome editing therapeutic prior to the
onset of pathology. To fully understand the potential of IUGE and in preparation for IND applications, rigorous
small and large animal studies are required to assess efficacy as well as fetal and maternal safety. The In
Utero Small and Large Animal Resource Core will provide the knowledge and technical expertise required to
design, implement and analyze in vivo gene editing therapies in mouse and large animal fetal models, including
nonhuman primates.
Terms: <Animal Model><Animal Models and Related Studies><Animals><Biodistribution><Birth><Body Tissues><Cell Therapy><Cerebellomedullary Cistern><Clinical Research><Clinical Study><Crab-Eating Macaque><Crab-Eating Monkey><Cynomolgus Monkey><Cynomolgus macaque><DNA Therapy><Data><Disease><Disorder><Dose><Early treatment><Fetal Lamb><Fetal Sheep><Fetal ovine><Fetal safety><Fetus><Future><Gene Delivery><Gene Transfer Clinical><Generalized Growth><Genes><Genetic Intervention><Gestation><Growth><Harvest><Hereditary Tyrosinemias><Human><Immune response><Immune system><Immunological response><Injections><Investigators><Knowledge><Lead><Letters><Liver><M fascicularis><M. fascicularis><MPS 1><MPS I><Macaca fascicularis><Mendelian disease><Mendelian disorder><Mendelian genetic disorder><Metabolic Diseases><Metabolic Disorder><Mice><Mice Mammals><Modeling><Modern Man><Morbidity><Morbidity - disease rate><Mothers><Mucopolysaccharidosis 1><Mucopolysaccharidosis I><Murine><Mus><Onset of illness><Organ><Ovine><Ovis><Parturition><Pathology><Pb element><Personal Satisfaction><Pregnancy><Preparation><Procedures><Progenitor Cells><Property><Proteins><Publishing><Research Personnel><Research Resources><Researchers><Resources><Safety><Services><Sheep><Structure of omphalomesenteric vein><Technical Expertise><Techniques><Technology><Therapeutic><Thesaurismosis><Time><Tissue Growth><Tissue Harvesting><Tissues><Toxic effect><Toxicities><Tyrosinemias><Umbilical vein><Vitelline Vein><Weight><alpha-L-iduronidase (IDA, IDUA) deficiency><alpha-L-iduronidase deficiency><animal resource><base editing><base editor><cell mediated therapies><cell-based therapeutic><cell-based therapy><cellular therapeutic><cellular therapy><cisterna magna><delivery vector><delivery vehicle><design><designing><determine efficacy><disease onset><disorder onset><early therapy><effective therapy><effective treatment><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><evaluate efficacy><examine efficacy><experience><fetal><gene repair therapy><gene therapy><gene-based therapy><gene-editing therapy><genetic therapy><genome editing><genome editing based therapy><genome editing therapy><genome editing treatment><genome editing-based therapeutics><genomic editing><genomic therapy><heavy metal Pb><heavy metal lead><hepatic body system><hepatic organ system><hepatic vein><host response><iduronidase deficiency disease><immune system response><immunoresponse><in utero><in vivo><information gathering><lipid based nanoparticle><lipid nanoparticle><maternal safety><maternal serum><maternal wellbeing><metabolism disorder><model of animal><monogenic disease><monogenic disorder><mortality><mouse model><mucopolysaccharide storage disease I><mucopolysaccharidosis (MPS) I><mucopolysaccharidosis type I><murine model><nano particle delivery><nanoparticle delivered><nanoparticle delivery><non-human primate><nonhuman primate><ontogeny><ovine animal model><ovine model><postnatal><pre-clinical study><preclinical study><prenatal><preparations><sheep model><single-gene disease><single-gene disorder><stem cells><technical skills><therapeutic editing><therapeutic genome editing><ultrasound><unborn><weights><well-being><wellbeing><α-L-iduronidase (IDA, IDUA) deficiency>