New Delivery Systems for Therapeutic Oligonucleotides

Antisense and triple helix-forming oligonucleotides (TFOs) have great potential as therapeutic agenspecifically block the expression of deleterious genes. We will develop novel delivery vehicles, tointernalization and membrane permeability of oligonucleotides. These compounds are polyaminolipids tcationic and lipophilic moieties, and they are designed to be biodegradable and relatively nontoxicutility of the potential uptake enhancers will be validated in a quantitative, anti-oncogene assay shave established sensitive in vitro assays to measure the inhibition of Epidermal Growth Factor Receexpression in glioblastoma cells. The candidate uptake enhancers will be coadministered with anti-EGany gain in the biological efficacy of the TFOs will be quantified. A variety of TFO and polyaminolitested. The toxicity and pharmacokinetic properties of the most effective formulation will be monitoThe most promising uptake enhancers will be tested for in vivo pharmacological activity in Phase IIprinciple, the approach should be of utility in optimizing the cellular delivery of not only oligonupieces of DNA for gene therapy.