4.7 Review

Cellular engineering of plant cells for improved therapeutic protein production

期刊

PLANT CELL REPORTS
卷 40, 期 7, 页码 1087-1099

出版社

SPRINGER
DOI: 10.1007/s00299-021-02693-6

关键词

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

资金

  1. Arkansas IDeA Network of Biomedical Research Excellence-Research Development Grant [P20GM103429]
  2. National Science Foundation [1605564]
  3. Arkansas Biosciences Institute
  4. Div Of Chem, Bioeng, Env, & Transp Sys
  5. Directorate For Engineering [1605564] Funding Source: National Science Foundation

向作者/读者索取更多资源

In vitro cultured plant cells, particularly the tobacco BY-2 cell, have shown promise as a bioproduction platform for therapeutic proteins. Despite progress in improving the plant cell culture system, challenges such as low productivity and non-human glycosylation remain. Modern molecular biology tools are being used to engineer plant cells for enhanced recombinant protein production.
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(R)), 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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