Open AccessOptimization of Non-Viral Gene Therapeutics Using Bilamellar Invaginated Vesicles
Author(s) -
Nancy Smyth Templeton
Publication year - 2011
Publication title -
journal of genetic syndromes and gene therapy
Language(s) - English
Resource type - Journals
ISSN - 2157-7412
DOI - 10.4172/2157-7412.s5-002
Subject(s) - biodistribution , in vivo , plasmid , gene delivery , genetic enhancement , dna , vesicle , liposome , computational biology , pharmacology , systemic administration , cancer research , biology , microbiology and biotechnology , chemistry , gene , biochemistry , membrane
Bilamellar invaginated vesicles (BIVs) are unique liposomal nanoparticles (NPs) that are highly efficient vehicles for intravenous (iv) delivery of encapsulated therapeutics including plasmid DNA. Systemic administration of therapeutics is required to effectively treat or cure metastatic cancer, certain cardiovascular diseases, and other acquired or inherited diseases. In addition to having extended half-life and stability in circulation, BIVs are nontoxic, nonimmunogenic, biodegradable and can be repeatedly administered without losing potency. Furthermore, BIVs encapsulating therapeutic agents can be modified to specifically enter the disease cells using small molecules that mimic beta turns incorporated on the surface of BIV complexes while focusing biodistribution by bypassing uptake in non-target organs and tissues using reversible masking. These modifications do not alter the unique properties of the BIV delivery system that provide for its robust treatment of disease demonstrated in small and large animal models and in Phase I clinical trials. This review will cover the unique properties of BIVs, including its fusogenic entry into cells and its ability to penetrate tight barriers in vivo. Methods to further improve the overall delivery-expression system including further purification of plasmid DNA to eliminate colanic acid from all current commercially produced preparations, and enhanced or prolonged expression provided by plasmid design will also be discussed.