Adenovirus-mediated gene delivery: Potential applications for gene and cell-based therapies in the new era of personalized medicine

Abstract

With rapid advances in understanding molecular pathogenesis of human diseases in the era of genome sciences and systems biology, it is anticipated that increasing numbers of therapeutic genes or targets will become available for targeted therapies. Despite numerous setbacks, efficacious gene and/or cell-based therapies still hold the great promise to revolutionize the clinical management of human diseases. It is wildly recognized that poor gene delivery is the limiting factor for most in vivo gene therapies. There has been a long-lasting interest in using viral vectors, especially adenoviral vectors, to deliver therapeutic genes for the past two decades. Among all currently available viral vectors, adenovirus is the most efficient gene delivery system in a broad range of cell and tissue types. The applications of adenoviral vectors in gene delivery have greatly increased in number and efficiency since their initial development. In fact, among over 2000 gene therapy clinical trials approved worldwide since 1989, a significant portion of the trials have utilized adenoviral vectors. This review aims to provide a comprehensive overview on the characteristics of adenoviral vectors, including adenoviral biology, approaches to engineering adenoviral vectors, and their applications in clinical and preclinical studies with an emphasis in the areas of cancer treatment, vaccination and regenerative medicine. Current challenges and future directions regarding the use of adenoviral vectors are also discussed. It is expected that the continued improvements in adenoviral vectors should provide great opportunities for cell and gene therapies to live up to its enormous potential in personalized medicine.

Long non‐coding RNA (lncRNA) H19 induces hepatic steatosis through activating MLXIPL and mTORC1 networks in hepatocytes

“…[29][30][31] Briefly, the full-length transcript of mouse H19 was PCR amplified for generating recombinant adenoviral plasmid pAd-H19 as described. [29][30][31] Briefly, the full-length transcript of mouse H19 was PCR amplified for generating recombinant adenoviral plasmid pAd-H19 as described.…”

Jagged1‐expressing adenovirus‐infected dendritic cells induce expansion of Foxp3+ regulatory T cells and alleviate T helper type 2‐mediated allergic asthma in mice

“…These vectors allow the transmission of genes to host nuclei but do not insert their genes into the host chromosome. Therefore, there is a low probability of disturbing vital cellular genes or processes . Today, replication‐competent adenoviral vectors have shown promising results in clinical trials .…”

“…Therefore, there is a low probability of disturbing vital cellular genes or processes. 34 Today, replication-competent adenoviral vectors have shown promising results in clinical trials. 35,36 On the other hand, as major contributors to the decision between immunity and tolerance, DCs are the focus of various immune interventions.…”

Bacteriophage lambda: The path from biology to theranostic agent

“…(c) Reprinted with permission from Dr. Sherwood Casjens (1998) 3 | BACTERIOPHAGES AS NANO-THERANOSTIC PLATFORMS The fundamental principles derived from in vitro studies have allowed cooptation of the viral assembly pathways toward engineering and construction of semisynthetic nanoparticles for potential therapeutic and diagnostic applications. While adenovirus and retroviral systems have made great strides as gene delivery vectors (Lee et al, 2017), bacteriophages offer many advantages over these as nanoparticle platforms; they are biocompatible, noninfectious in humans, essentially nontoxic to eukaryotic cells and are tolerant of genetic and chemical manipulation (Clark & March, 2006;Koudelka, Pitek, Manchester, & Steinmetz, 2015;Rohevie et al, 2016). Phage particles have defined sizes and shapes, are soluble, monodisperse, and allow for symmetric and defined presentation of surface ligands (Fokine & Rossmann, 2014;Veesler & Johnson, 2012).…”