![]() ![]() To date, viral vectors are still the predominant type reported in clinical trials with adenoviral being the most used (18.5% of the trials), while naked plasmid DNA (pDNA) accounts for 14.9% ( Wiley 2019). 1 Vectors used in gene therapy can be classified as viral (e.g., adenoviruses, retroviruses, lentiviruses) or non-viral (e.g., plasmid DNA, RNA). The area has attracted an ongoing interest by the scientific community, as can be inferred by the more than 3,000 clinical trials reported since 1989 ( Wiley 2019). Gene therapy is currently defined as the delivery of vectors carrying extra genetic material into cells, with the aim of treating or curing a disorder by modification of endogenous gene expression ( Kay 2011). Broad and comprehensive analysis of the progress and developments on the nucleic acid biopharmaceutical field can be found in recent reviews (e.g., Prazeres and Monteiro 2014 Uludag et al., 2019). Specifically in the area of nucleic acid based products, several types are reported, namely antisense oligonucleotides, aptamers, modified RNA molecules, small interfering RNAs, gene therapy vectors and DNA or RNA vaccines ( Walsh 2018). Biopharmaceuticals encompass a wide range of products such as antibodies (which currently hold the highest number of product approvals), recombinant enzymes, cell-based therapies and nucleic-acid based products, among others. Since then, the field has been marked by a continuous increase in the number and types of biopharmaceuticals developed and marketed to treat diseases such as cancer, inflammation-related conditions, hemophilia and diabetes. The modern era of biopharmaceuticals started with the approval of Humulin, a therapeutic recombinant insulin developed by Genentech that was approved by the Food and Drug Administration (FDA) and commercialized by Eli Lilly in 1982 ( Walsh, 2003 Rader 2008). One of the main advantages of biopharmaceutical products is their higher specificity and activity in comparison to conventional drugs. This review summarizes the different methods developed so far, focusing not only on the purification method itself but also on its dependence on the upstream production strategy used.īiopharmaceuticals are classically defined as a pharmaceutical drug with active agents of biological origin that are manufactured by biotechnological processes. In minicircle purification, the characteristics of the strain and parental plasmid used have a high impact and strongly affect the purification strategy that can be applied. Several strategies have been proposed over the years to meet the challenge of purifying and obtaining high quality minicircles in compliance with the regulatory guidelines for therapeutic use. ![]() The production process results thus in a complex mixture, which hinders the isolation of minicircle molecules from other DNA molecules. These vectors are plasmid-derived circular DNA molecules that are obtained in vivo in Escherichia coli by the intramolecular recombination of a parental plasmid, which generates a minicircle containing the eukaryotic therapeutic cassette of interest and a miniplasmid containing the prokaryotic backbone. Minicircles are non-viral delivery vectors with promising features for biopharmaceutical applications. 2Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal.1iBB- Institute for Bioengineering and Biosciences, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal. ![]()
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