Cellular engineering of plant cells for improved therapeutic protein production.

Publisher: Springer Country of Publication: Germany NLM ID: 9880970 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-203X (Electronic) Linking ISSN: 07217714 NLM ISO Abbreviation: Plant Cell Rep Subsets: MEDLINE

Original Publication: Berlin ; New York : Springer, 1981-

Molecular Biology/*methods ; Plant Cells/*physiology ; Recombinant Proteins/*genetics; Cell Line ; Cells, Cultured ; Gene Editing ; Glycosylation ; Humans ; Plants, Genetically Modified ; Protein Engineering/methods ; RNA Interference ; Recombinant Proteins/metabolism ; Recombinant Proteins/pharmacology

In vitro cultured plant cells, in particular the tobacco BY-2 cell, have demonstrated their potential to provide a promising bioproduction platform for therapeutic proteins by integrating the merits of whole-plant cultivation systems with those of microbial and mammalian cell cultures. Over the past three decades, substantial progress has been made in improving the plant cell culture system, resulting in a few commercial success cases, such as taliglucerase alfa (Elelyso ^® ), the first FDA-approved recombinant pharmaceutical protein derived from plant cells. However, compared to the major expression hosts (bacteria, yeast, and mammalian cells), plant cells are still largely underutilized, mainly due to low productivity and non-human glycosylation. Modern molecular biology tools, in particular RNAi and the latest genome editing technology CRISPR/Cas9, have been used to modulate the genome of plant cells to create new cell lines that exhibit desired "traits" for producing therapeutic proteins. This review highlights the recent advances in cellular engineering of plant cells towards improved recombinant protein production, including creating cell lines with deficient protease levels or humanized glycosylation, and considers potential development in the future.

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P20 GM103429 United States GM NIGMS NIH HHS; P20GM103429 NIH-INBRE; 1605564 National Science Foundation

Keywords: Cellular engineering; Genome editing; Glycoengineering; Plant cell culture; RNA interference; Recombinant proteins

0 (Recombinant Proteins)

Date Created: 20210410 Date Completed: 20210716 Latest Revision: 20210716

20221213

PMC8035600

10.1007/s00299-021-02693-6

33837823