Periodic Reporting for period 1 - SUPRO-GEN (Supramolecular Polyamine Gene Vectors for Cancer Therapy)
Período documentado: 2021-09-01 hasta 2024-02-29
Gene therapy represents a promising therapeutic approach to treat various conditions, including cancer. Oftentimes, they utilize viral vectors to deliver nucleic acid cargo into target cells for gene silencing or editing profiting from the capacity of the virus to integrate in the host genome. However, inherent safety risks and limitations of viral vectors present barriers to further development and medical translation. To address this challenge, the SUPRO-GEN consortium aims to develop non-viral vectors based on positively charged polymers and lipids capable of electrostatically loading complex nucleic acids and targeted delivery to cancerous cells. To bring this technology to broad use and improve existing and future treatments, SUPRO-GEN researchers will extensively characterize and optimize engineered polyamine-lipid vectors for preclinical validation. These developments will further the targeting, potency, and efficacy capacities of cancer therapeutics.
During this first reporting period, preparation and extensive characterization of several non-viral vector platforms based on polyallylamine hydrochloride (PAH) and polyplexes formed with nucleic acids was performed. By functionalizing the vectors with oleic acid, polyethylene glycol (PEG), and/or dextran, researchers aim to optimize the synthesis conditions and formulation parameters. Understanding the transfection efficacy and fate of polyplexes under in vitro and in vivo conditions, including cytotoxicity and biodistribution, provides proof-of-concept results supporting their therapeutic potential. These results so far have generated three publications, with several more expected. Research has been presented in international conferences. SUPROGEN activities have been carried out through the secondments of Early stage and Experience researchers between European and non-European institutions.
The SUPRO-GEN project has thus far worked on the development of new non-viral vectors with efficient transfection activity for gene therapy. Such next-generation vectors demonstrate potential as a therapeutic for cancers and other diseases, which would lead to improved patient outcomes and help to the translation of gene therapies to the market Furthermore, this project facilitates a collaborative interdisciplinary and international research environment, through the exchange of skills and knowledge during secondments, meetings, and other training activities that help to develop scientific and complementary skills among secondees, specially early stage researchers.