Plasmid Biopharmaceuticals

Abstract

Plasmids are currently an indispensable molecular tool in life science research and a central asset for the modern biotechnology industry, supporting its mission to produce pharmaceutical proteins, antibodies, vaccines, industrial enzymes, and molecular diagnostics, to name a few key products. Furthermore, plasmids have gradually stepped up in the past 20 years as useful biopharmaceuticals in the context of gene therapy and DNA vaccination interventions. This review provides a concise coverage of the scientific progress that has been made since the emergence of what are called today plasmid biopharmaceuticals. The most relevant topics are discussed to provide researchers with an updated overview of the field. A brief outline of the initial breakthroughs and innovations is followed by a discussion of the motivation behind the medical uses of plasmids in the context of therapeutic and prophylactic interventions. The molecular characteristics and rationale underlying the design of plasmid vectors as gene transfer agents are described and a description of the most important methods used to deliver plasmid biopharmaceuticals in vivo (gene gun, electroporation, cationic lipids and polymers, and micro- and nanoparticles) is provided. The major safety issues (integration and autoimmunity) surrounding the use of plasmid biopharmaceuticals is discussed next. Aspects related to the large-scale manufacturing are also covered, and reference is made to the plasmid products that have received marketing authorization as of today.

An escalating dose study to assess the safety, tolerability and immunogenicity of a Herpes Simplex Virus DNA vaccine, COR-1

“…A large number of DNA vaccines have undergone clinical trial and their general safety demonstrated 18 . Consistent with those studies, this Phase I clinical trial clearly demonstrates that 3 intradermal immunizations with COR-1 is safe and well-tolerated in humans at doses up to 1 mg, with no vaccine-related moderate or severe TEAEs or SAEs observed.…”

A Cautionary Tale of Cross-Contamination Among Plasmids from Commercial Suppliers

“…Naturally occurring plasmids mediate a variety of biological functions including bacterial conjugation, transfer of disease-causing virulence genes and transfer of resistance genes to various detrimental environmental factors, such as antibiotics, radiation and heavy metals. With the discovery of restriction enzymes [2,3] and subsequent development of recombinant DNA technology [4], plasmids have become versatile tools in basic biological research and biotechnology development for biomedical, agricultural and industrial applications [5][6][7][8][9][10][11]. With the advent of de novo DNA synthesis [12] and the decreasing cost and rising efficiency of relevant technologies, more and more researchers have switched to de novo synthesis of their desired plasmids to save resources and time required for traditional cloning methods [13,14].…”

Progress in Neoantigen Targeted Cancer Immunotherapies

“…DNA vaccine is stable, safe in handling, cost-efficient and easy to manufacture (Prazeres and Monteiro, 2014). Importantly, DNA vaccine can activate both CD4+ and CD8+ T cell response, as well as innate immune response due to the recognition of double stranded DNA structure by cytosolic sensors (Tang and Pietersz, 2009;Ori et al, 2017).…”