Abstract

The central theme of this program is to exploit recent advances in basic science for t he development of innovative gene therapy strategies, especially for metabolic disorders causing mental retardation. The program is highly focused on identifying and resolving the barriers to clinical gene therapy. In this period, five projects aim to exploit recent innovations t hat would enhance gene delivery and expression or actually correct genomic mutations in vivo. These projects are: Therapy for Hyperammonemia with Genetically-Engineered Bacteria (Tuchman). Adeno-Associated Virus Vector Treatment of Spinocerebellar Ataxia (McIvor) Chimeraplasty for Mutations Associated with Mental Retardation (Kren) Sleeping Beauty Transposon for Gene Therapy (Hackett) Lentiviral Ex Vivo Hematopoietic Stem Cell Gene Therapy for Mucopolysaccharidosis Type 1 (Whitley) The projects utilize a number of models of human metabolic disorders causing brain disease, notably, murine models of mucopolysaccharidosis, hyperammonemia, phenylketonuria and spinocerebellar ataxia. The program share core facilities for administration, microchemicals, quantitative PCR, hematopoietic cell processing, animal resources and viral vector production.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
3P01HD032652-08S1
Application #
6554887
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Oster-Granite, Mary Lou
Project Start
1995-01-10
Project End
2002-12-31
Budget Start
2002-01-01
Budget End
2002-12-31
Support Year
8
Fiscal Year
2002
Total Cost
$6,727
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Pediatrics
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Ou, Li; Przybilla, Michael J; Whitley, Chester B (2018) Metabolomics profiling reveals profound metabolic impairments in mice and patients with Sandhoff disease. Mol Genet Metab :
Ou, L; Przybilla, M J; Whitley, C B (2018) SAAMP 2.0: An algorithm to predict genotype-phenotype correlation of lysosomal storage diseases. Clin Genet 93:1008-1014
Ou, Li; Przybilla, Michael J; Whitley, Chester B (2017) Phenotype prediction for mucopolysaccharidosis type I by in silico analysis. Orphanet J Rare Dis 12:125
Hyland, Kendra A; Aronovich, Elena L; Olson, Erik R et al. (2017) Transgene Expression in Dogs After Liver-Directed Hydrodynamic Delivery of Sleeping Beauty Transposons Using Balloon Catheters. Hum Gene Ther 28:541-550
Aronovich, Elena L; Hyland, Kendra A; Hall, Bryan C et al. (2017) Prolonged Expression of Secreted Enzymes in Dogs After Liver-Directed Delivery of Sleeping Beauty Transposons: Implications for Non-Viral Gene Therapy of Systemic Disease. Hum Gene Ther 28:551-564
Ou, Li; Przybilla, Michael J; Whitley, Chester B (2017) Proteomic analysis of mucopolysaccharidosis I mouse brain with two-dimensional polyacrylamide gel electrophoresis. Mol Genet Metab 120:101-110
Verhaart, Ingrid E C; Robertson, Agata; Wilson, Ian J et al. (2017) Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophy - a literature review. Orphanet J Rare Dis 12:124
Ou, Li; Przybilla, Michael J; Koniar, Brenda L et al. (2016) Elements of lentiviral vector design toward gene therapy for treating mucopolysaccharidosis I. Mol Genet Metab Rep 8:87-93
Aronovich, Elena L; Hackett, Perry B (2015) Lysosomal storage disease: gene therapy on both sides of the blood-brain barrier. Mol Genet Metab 114:83-93
Satzer, David; DiBartolomeo, Christina; Ritchie, Michael M et al. (2015) Assessment of dysmyelination with RAFFn MRI: application to murine MPS I. PLoS One 10:e0116788

Showing the most recent 10 out of 92 publications