The central hypothesis of this proposal is that site and sequence specific insertion of genes into eukaryotic chromosomes can be carried out with Tn7 transpositional proteins. The overall objective is to establish a biological basis for gene therapy based on the use of transposon Tn7 proteins. Tn7 was selected for its ability to integrate into a DNA sequence with specificity and efficiency. Preliminary data support a hypothesis that Tn7 based insertion could provide a safe and efficient method to incorporate therapeutic genes into chromosomes. The central hypothesis will be tested in three Specific Aims: 1.Will Tn7 proteins transposed into eukaryotic targets in vitro? 2. Will Tn7 proteins transpose into eukaryotic targets in vivo? 3. Will Tn7 transposition disrupt normal glutamine-fructose-6-phosphate transaminase (GFPT) expression?

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
1R01CA076290-01A1
Application #
2745214
Study Section
Special Emphasis Panel (ZRG2-ET-2 (01))
Program Officer
Wolpert, Mary K
Project Start
1999-01-01
Project End
2001-12-31
Budget Start
1999-01-01
Budget End
1999-12-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Thomas Jefferson University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
061197161
City
Philadelphia
State
PA
Country
United States
Zip Code
19107
Wickstrom, Eric (2015) DNA and RNA derivatives to optimize distribution and delivery. Adv Drug Deliv Rev 87:25-34
Chakrabarti, Atis; Desai, Priyanka; Wickstrom, Eric (2004) Transposon Tn7 protein TnsD binding to Escherichia coli attTn7 DNA and its eukaryotic orthologs. Biochemistry 43:2941-6