Completion of sequencing of the human and of bacterial genomes has made it possible to apply the principle of oligonucleotide hybridization competition to the inhibition of nefarious genic expression. We shall focus our efforts on three targets: l) M. tuberculosis, with its uniquely constructed mycocerosic outer cell wall; 2) Cystic Fibrosis, in which for our novel oligonucleotide insertion technique we must pin down the extent of insertion. Present estimates, as a result of over thousand sequencings, are that insertion occurs in 10-25 percent of delta508 mRNA molecules; 3) Huntington's Disease, requiring further studies to firm up our finding of inhibition of expression of Huntington protein in tissue cultures from patients with this disease, using derivatives of antisense oligonucleotides.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI060872-01
Application #
6809691
Study Section
Special Emphasis Panel (ZRG1-IDM-E (03))
Program Officer
Laughon, Barbara E
Project Start
2004-06-15
Project End
2007-05-31
Budget Start
2004-06-15
Budget End
2005-05-31
Support Year
1
Fiscal Year
2004
Total Cost
$420,967
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
073130411
City
Boston
State
MA
Country
United States
Zip Code
02199
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Tabatadze, David; Zamecnik, Paul; Yanachkov, Ivan et al. (2008) A novel thymidine phosphoramidite synthon for incorporation of internucleoside phosphate linkers during automated oligodeoxynucleotide synthesis. Nucleosides Nucleotides Nucleic Acids 27:157-72
Zhang, Surong; Metelev, Valeri; Tabatadze, David et al. (2008) Near-infrared fluorescent oligodeoxyribonucleotide reporters for sensing NF-kappaB DNA interactions in vitro. Oligonucleotides 18:235-43
Harth, Gunter; Zamecnik, Paul C; Tabatadze, David et al. (2007) Hairpin extensions enhance the efficacy of mycolyl transferase-specific antisense oligonucleotides targeting Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 104:7199-204
Elmaleh, D R; Fischman, A J; Tawakol, A et al. (2006) Detection of inflamed atherosclerotic lesions with diadenosine-5',5'''-P1,P4-tetraphosphate (Ap4A) and positron-emission tomography. Proc Natl Acad Sci U S A 103:15992-6