NUCLEAR TARGETING OF OLIGONUCLEOTIDE-PEPTIDE CONJUGATES

Award Information
Agency:
Department of Health and Human Services
Amount:
$499,629.00
Program:
SBIR
Contract:
N/A
Solitcitation Year:
N/A
Solicitation Number:
N/A
Branch:
N/A
Award Year:
1992
Phase:
Phase II
Agency Tracking Number:
13637
Solicitation Topic Code:
N/A
Small Business Information
Microprobe Corp.
1725 220th St Se #104, Bothell, WA, 98021
Hubzone Owned:
N
Woman Owned:
N
Socially and Economically Disadvantaged:
N
Duns:
N/A
Principal Investigator
 Michael W Reed
 (206) 485-8566
Business Contact
Phone: () -
Research Institution
N/A
Abstract
THIS PHASE I STUDY WILL EXPLORE THE THERAPEUTIC POSSIBILITIES OF ANTISENSE OLIGODEOXYNUCLEOTIDES THAT HAVE BEEN COVALENTLY CONJUGATED TO SIGNAL PEPTIDES THAT CAN DIRECT THE TRANSPORT OF PROTEINS INTO THE NUCLEUS. IN RECENT YEARS, 16 PEPTIDE SEQUENCES WITH NUCLEAR TARGETING PROPERTIES HAVE BEEN IDENTIFIED. THREE OF THESE PEPTIDES WILL BE SYNTHESIZED AND CONJUGATED TO ANTISENSE OLIGODEOXYNUCLEOTIDES THAT INTERFERE WITH SURFACE ANTIGEN PRODUCTION IN HEPATITIS B VIRUS. EACH PEPTIDE-OLIGONUCLEOTIDE CONJUGATE WILL BE LABELED WITH RADIOACTIVE PHOSPHORUS AND TESTED FOR ITS ABILITY TO LOCALIZE TO THE NUCLEUS IN A CELL-FREE PREPARATION OF RAT LIVER NUCLEI. UNMODIFIED OLIGONUCLEOTIDES OF VARIOUS LENGTHS WILL ALSO BE RADIOLABELED, AND THEIR RATE OF NUCLEARUPTAKE/DIFFUSION WILL BE EVALUATED. THE PEPTIDE-OLIGONUCLEOTIDE CONJUGATES WILL ALSO BE EXAMINED FOR IMPROVED ANTISENSE EFFECT IN HEPATITIS B-INFECTED (HEP3B) CELLS. THESE EXPERIMENTS WILL CONSTITUTE A FEASIBILITY STUDY FOR THE DEVELOPMENT OF PEPTIDE-OLIGONUCLEOTIDE CONJUGATES THAT COULD BE IMPORTANT FOR THE THERAPEUTIC TREATMENT OF DISEASESCAUSED BY INFECTION WITH HUMAN IMMUNODEFICIENCY VIRUS, HEPATITIS B, HERPES VIRUSES, OR OTHER VIRUSES.

* information listed above is at the time of submission.

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