Chapter 34 : Plasmid Biopharmaceuticals

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The contributions of plasmids to biology and their impact in biotechnology and discovery have been immense. Together with restriction enzymes, plasmids were one of the key molecular tools at the heart of the invention and development of DNA cloning and recombinant DNA by Hebert Boyer and Stanley Cohen ( ). These fundamental technologies shaped molecular biology and paved the way to the development of the modern, multibillion dollar biotechnology industry ( ). The ability to produce unlimited amounts of proteins via the cloning of the corresponding gene into a plasmid and subsequent transformation of a microbial host made it possible to develop a range of medically and industrially relevant products and applications. The development of molecular diagnostics and protein biopharmaceuticals, for example, would have been impossible without plasmids. However, few would have suspected in the earlier years of recombinant DNA that plasmids could one day assume the role of biopharmaceuticals themselves ( ).

Citation: Prazeres D, Monteiro G. 2015. Plasmid Biopharmaceuticals, p 669-688. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0022-2014
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Figure 1

Plasmid biopharmaceuticals: the formative years.

Citation: Prazeres D, Monteiro G. 2015. Plasmid Biopharmaceuticals, p 669-688. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0022-2014
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Figure 2

Basic physical characteristics of plasmid vectors. Data presented is for 2,000- to 10,000-bp plasmids with a typical degree of supercoiling (Prazeres, 2011). Image is reprinted with permission from reference with permission from Wiley. Copyright 2011, John Wiley and Sons, Inc.

Citation: Prazeres D, Monteiro G. 2015. Plasmid Biopharmaceuticals, p 669-688. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0022-2014
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Figure 3

(A) Schematic representation of the recombination of a parental plasmid (PP) into a minicircle (MC) and a miniplasmid (MP) via the excision of the eukaryotic expression cassette that is flanked by two multimer resolution sites (MRS). (B) Agarose gel electrophoresis showing a parental plasmid before the induction of recombination (BR) and minicircle and miniplasmid species after recombination (AR). Abbreviations: ORI, origin of replication; GOI, gene of interest.

Citation: Prazeres D, Monteiro G. 2015. Plasmid Biopharmaceuticals, p 669-688. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0022-2014
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Figure 4

The intracellular barriers to plasmid-based gene transfer. In their journey to the nucleus, plasmids have to cross the phospholipidic cell membrane through endocytosis (1), escape entrapment and degradation in endosomes and lysosomes (2), survive degradation by cytosolic nucleases, traffic the overcrowded cytoplasm (3), and translocate across the nuclear envelope (4).

Citation: Prazeres D, Monteiro G. 2015. Plasmid Biopharmaceuticals, p 669-688. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0022-2014
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Figure 5

plasmid delivery. Plasmid DNA can be combined and formulated with buffers, stabilizers, and inorganic or organic matrices and molecules to produce: (i) a saline solution of plasmid, (ii) gold particles coated with plasmid, (iii) plasmids complexed with cationic lipids or polymers, (iv) polymeric microparticles with encapsulated or surface-adsorbed plasmid, or (v) nanoparticles of compacted plasmid.

Citation: Prazeres D, Monteiro G. 2015. Plasmid Biopharmaceuticals, p 669-688. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0022-2014
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Figure 6

An overview of the different activities and steps involved in the manufacturing of plasmid biopharmaceuticals.

Citation: Prazeres D, Monteiro G. 2015. Plasmid Biopharmaceuticals, p 669-688. In Tolmasky M, Alonso J (ed), Plasmids: Biology and Impact in Biotechnology and Discovery. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.PLAS-0022-2014
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