On the in vivo kinetics of gene delivery vectors

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. ContextGene delivery vectors consist of a broad spectrum of natural or synthetically produced vehicles that represent one out of the three essential aspects of each gene delivery system, without which the successful and effective (in terms of the clinical translation) delivery of therapeutic nucleic acids to a diseased mal- or sub-functioning cell would be impossible. ObjectiveThe presentation and evaluation of the in vivo pharmacokinetic behavior of different viral and non viral gene delivery vectors including a wide review of their mechanism of action, possible safety concerns as well as the promise each holds for future applications. Data SourcesA systematic literature search was conducted using the electronic databases PubMed, Google Scholar and Science Direct while also utilizing the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The keywords included in the research effort were the following: viral vectors, adeno-associated viral vectors, non viral vectors, oncolytic vectors, novel gene delivery vectors, pharmacokinetics of viral vectors, retroviral vectors, recombinant adeno-associated viral vectors, toxicity of gene delivery vectors, Vitravene, Oncorene, Approved gene delivery vectors. Study SelectionCase studies and review articles published in scientifically accepted, high impact factor journals focused on gene delivery vectors and published in English between the years 1999 to 2021 in order to include the most significant findings in terms of both well established data through the years as well as the most recent breakthroughs in terms of preclinical and clinical application. Data ExtractionEssential information were retrieved regarding the various types, behavior, mechanisms of action, safety and in vivo pharmacokinetic behavior of the most prominent viral and non viral gene delivery vectors. ResultsOf a total of 186 records a total of 36 full text articles were reviewed covering a total of 92 case studies and review articles on the topic of the pharmacokinetic behavior of gene delivery vectors including promising future considerations for their clinical use. LimitationsThe outcome of this review article was limited by findings that were shared between different articles published in a variety of literary platforms as well as from papers that lacked sufficient details in order to be included. ConclusionThis scoping review has examined what is currently known and recently discovered regarding the wholesome of the aspects of utilizing specific gene delivery vehicles for a variety of different therapeutic purposes. Their nature, characteristics, as well as their individual action once inserted into the organism and/or in a variety of different in vivo experiments was examined and the implication of their use regarding their shortcomings and possible dangers, as well as their therapeutic advantages and probable future applications were weighted.