On the in vivo kinetics of gene delivery vectors

Abstract

Gene therapy is the most promising strategy for treating a number of diseases at their most fundamental, genetic level, and it has a wide range of promising clinical and emerging preclinical uses in both the clinic and the laboratory. Gene therapy systems are composed of three fundamental components, with the delivery platform being responsible for the protection and successful delivery of the incorporated therapeutic nucleic acid sequences. A successful delivery platform is critical in the achievement of a therapeutic outcome, and an effective delivery platform is essential in achieving this. A variety of different gene delivery platforms - vectors - are evaluated in this dissertation in terms of their nature, mechanism of action, potential applications, and safety. Of particular importance is the evaluation of their post-delivery pharmacokinetic and adverse drug-metabolite profiles. The different types of vectors, including viral, non-viral, and alternative vectors, are discussed separately in each chapter, while important issues related to the incorporation of these vectors into clinical practice are discussed as well, including the topics of vector development and manufacturing, as well as the current regulatory landscape and efforts to improve it, and finally their prospects for the immediate future.

RNA Combined with Nanoformulation to Advance Therapeutic Technologies

“…Viral vectors, which make use of viruses' ability to transfer genetic information into host cells, have shown promise in gene therapy systems [117]. Numerous altered viral vector genomes have been created, such as lentiviruses, herpes viruses, adenoviruses, adenoassociated viruses, retroviruses, human foamy viruses (HFVs), and herpes viruses [118,119] These modified genomes have certain limitations, including immunogenicity, toxin production, insertional mutagenesis, and constraints in transgenic capacity size [120,121]. Recent advancements have led to the design of viral vectors with specific receptors for the transfer of transgenes to non-natural target cells, a concept known as retargeting [120].…”