cihr_grants: 170617
This data as json
| external_id | title | project_lead_name | co_researchers | institution | province | country | competition_year | award_amount | program | program_type | theme | research_subject | keywords | abstract | duration | source_url |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 170617 | Development of chemically modified oligonucleotide therapeutics and mechanistic probes | Damha Masad J | Damha, Masad J | McGill University | Québec | Canada | 200809 | 349989.0 | Operating Grant | Operating Grants | Biomedical | Infection and Immunity | Anticancer And Antiviral Therapy; Biochemistry; Gene Target Knockdown; Oligonucleotide Therapeutics; Rnai And Antisense; Structural Studies On Nucleic Acids | RNA interference (RNAi) is a natural cellular mechanism for selectively silencing the expression of genes via targeted mRNA degradation, preventing gene-coded protein production. Synthetic oligonucleotides (ONs) that activate the RNAi pathway have tremendous potential for functional genomics, drug discovery through in vivo target validation, and novel classes of specific gene-silencing therapeutics. Inherent characteristics of ONs have hampered their progression from the laboratory to the clinic to treat diseases. As a result, chemical modification of these molecules to improve their specificity, potency, stability and pharmacodynamics is currently a hot topic and a major focus of our research activities. Our laboratory is developing chemically modified ONs that try to address several identified shortcomings of earlier generation drug candidates. The objectives of this grant proposal are to 1] advance the development of more effective and more specific oligonucleotide-based therapies; and 2] to deepen our understanding of the biochemical properties of key enzymes implicated in the mechanism of action of nucleic acid-based drugs. Thus, this proposal describes the design of novel chemically-modified antisense and small interfering RNA (siRNA); new chemistry that enhances the bioavailability and uptake oligonucleotides to target cells; and the evaluation of oligonucleotides comprising 2'-fluoroarabinose sugars as anti-tumor and anti-viral agents. The experimental plan combines chemical synthesis, physicochemical studies (NMR, CD, UV), cell based assays, etc, all built on a foundation of progress during 2005-2008 in developing modified oligonucleotides as gene silencing agents. The proposed work exposes students to nucleic acid chemistry and biology, analytical skills, and to strategies designed to develop candidate molecules into useful drugs. | 3 yrs 0 mth | https://webapps.cihr-irsc.gc.ca/decisions/p/project_details.html?applId=170617&lang=en |