Biomaterials for Gene Delivery  Atelocollagen-mediated Controlled Release of Molecular Medicines

Takahiro      Ochiya; Shunji      Nagahara; Akihiko      Sano; Hirosh      Itoh; Masaaki      Terada

Abstract

Over the last decade, increasing attention has been paid to the development of systems to deliver drugs for long periods at controlled rates. Some of these systems can deliver drugs continuously for over one year. However, little effort has been given to developing systems for the controlled release of nucleic acids. Recently, a novel gene transfer method which allows prolonged release and expression of plasmid DNA in vivo in normal adult animals was established. In this system, a biocompatible natural polymer such as collagen or its derivatives acts as the carrier for the delivery of DNA vectors. The biomaterial carrying the plasmid DNA was administered into animals and, once introduced, gradually released plasmid DNA in vivo. A single injection of plasmid DNA_biomaterial produced physiologically significant levels of gene-encoding proteins in the local_systemic circulation of animals and resulted in prolonged biological effects. These results suggest that the biomaterials carrying plasmid DNA may enhance the clinical potency of plasmid-based gene transfer, facilitating a more effective and long-term use of naked plasmid vectors for gene therapy. Furthermore, the biomaterials can be removed surgically, minimizing the effect of gene products if some unexpected side effects should be observed after application. The application of these systems to expand the bioavailability of molecular medicine, including antisense oligonucleotides and adenovirus vectors, and to aid in stem cell transplantation in the context of DNA-based tissue engineering will be discussed.

Keywords: Atelocollagen mediated, naked plasmid vectors, stem cell transplantation, human genome project, cationic liposomes, DNA gelatin nanospheres, atelocollagen implanted, fibroblast growth factor, adenovirus vectors, cationic amphiphiles