PASADENA, Calif., July 24, 2003 (PRIMEZONE) -- Insert Therapeutics, Inc. announced that it has been awarded a Phase I Flexible System to Advance Innovative Research (FLAIR) grant from the National Cancer Institute. The grant will be used to support the development of Insert's non-viral nucleic acid delivery system (Cyclosert(tm)) for targeted systemic delivery of the Interferon-alpha (IFN) gene to tumors.
The IFN protein and its modified derivatives have been FDA-approved for treating various types of cancers. The protein inhibits cancer cell growth through a variety of mechanisms including reducing expression of certain oncogenes and angiogenic factors as well as stimulating certain tumor suppressor genes. Nevertheless, the IFN protein and its derivatives are subject to degradation by proteases. This leads to a short in vivo half-life requiring frequent administrations or to fluctuations in steady state plasma levels that can diminish its effectiveness. A gene therapy approach capable of providing a continuous production and release of the IFN protein could overcome these limitations of protein therapeutics.
A critical component to successful nucleic acid based therapy is the safe and effective delivery of the nucleic acid therapeutic to the target tissue. To date, two main approaches (viral and non-viral systems) have been used. Insert has made significant progress in overcoming many of the limitations in systemic, non-viral delivery vectors. Insert's proprietary Cyclosert(tm) delivery system involves two components. The first is a linear, cyclodextrin-containing polycation. Already shown to be non-immunogenic, non-toxic, stable in vivo and amenable to large-scale production, Cyclosert self-assembles with nucleic acids by electrostatic interactions to form colloidal DNA-containing nanoparticles. Cyclosert has been shown to protect the nucleic acid, whether short single-stranded oligonucleotides or large plasmids, from nuclease degradation.
The second component of the Cyclosert delivery system is a modifying agent that incorporates a terminal adamantane capable of forming inclusion complexes with cyclodextrin molecules in the Cyclosert polymer backbone. This component self-assembles with the nucleic acid-containing particles to modify their surface properties, making them suitable for systemic delivery. Targeting ligands such as transferrin have been incorporated into the modifying agent to target the delivery of nucleic acids to specific tissues or cell types, including tumor cells. The fully formulated Cyclosert-DNA polyplexes have been shown to safely deliver DNA to tumor cells after intravenous injection, with subsequent expression.
"The FLAIR Grant will provide the opportunity for the scientists at Insert to significantly enhance their understanding of systemic, non-viral gene delivery," said Caltech Chemical Engineering Professor and founder of Insert Therapeutics Mark E. Davis, Ph.D.
Cyclosert(tm) Technology
Insert's patented drug delivery platform is based on small cyclic repeating molecules of glucose called cyclodextrins. Insert has developed modified cyclodextrins as building blocks of an entirely new proprietary class of materials, linear cyclodextrin-containing polymers, which Insert calls its Cyclosert technology. Animal studies have confirmed that Cyclosert polymers are non-toxic and non-immunogenic, even after repeated administration. In addition to facilitating the targeted delivery of nucleic acids, Insert has conjugated Cyclosert with a small-molecule anti-cancer agent, resulting in significant improvement in the solubility, stability, in vitro toxicity, and in vivo anti-tumor efficacy of the compound.
INSERT THERAPEUTICS, INC.
Insert Therapeutics, Inc., a privately held biopharmaceutical delivery company, is using its proprietary and entirely new polymeric delivery system, Cyclosert(tm), to design, develop and commercialize drug-delivery-enhanced small-molecule therapeutics and nucleic acids. The company is pursuing this goal through its internal research and development and also through collaborations and partnerships with pharmaceutical and biotechnology companies. For more information, visit www.insertt.com.