Monoclonal antibody manufacturing in transgenic plants — myths and realities

Hood, Elizabeth E.; Woodard, Susan L.; Horn, Michael E.

doi:10.1016/s0958-1669(02)00351-8

Cited by 147 publications

(79 citation statements)

References 10 publications

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“…Cereal seeds are likely to be the most suitable platform for deployment in such areas, because the infrastructure for large-scale cultivation and harvesting is already in place, and the dry seeds favor product stability (21). Maize is particularly attractive, because it has been developed as a commercial platform for recombinant protein production by a number of companies, and its success as a production system for pharmaceutical proteins is widely documented (22)(23)(24).…”

mentioning

confidence: 99%

Cost-effective production of a vaginal protein microbicide to prevent HIV transmission

Ramessar

Rademacher

Sack

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

150

124

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A series of small-molecule microbicides has been developed for vaginal delivery to prevent heterosexual HIV transmission, but results from human clinical trials have been disappointing. Proteinbased microbicides, such as HIV-specific monoclonal antibodies, have been considered as an alternative approach. Despite their promising safety profile and efficacy, the major drawback of such molecules is the economy of large-scale production in mammalian cells, the current system of choice. Here, we show that an alternative biomanufacturing platform is now available for one of the most promising anti-HIV antibodies (2G12). Our data show that the HIV-neutralization capability of the antibody is equal to or superior to that of the same antibody produced in CHO cells. We conclude that this protein production system may provide a means to achieve microbicide ingredient manufacture at costs that would allow product introduction and manufacture in the developing world.

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mentioning

confidence: 99%

Cost-effective production of a vaginal protein microbicide to prevent HIV transmission

Ramessar

Rademacher

Sack

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

150

124

View full text Add to dashboard Cite

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“…Previous studies have shown that the use of transgenic plants for recombinant protein production often results in low yields (Kermode, 2006). For some pharmaceutical proteins expressed in plant systems, yields have varied from 0.01% to 1% of TSP (Hood et al, 2002), and have even been as low as 0.0001% of TSP . Thus, one of the key challenges for recombinant protein production in transgenic plants is the employment of effective strategies to enhance expression levels, which is a requirement for economic effi ciency (Hood et al, 2002;Fischer et al, 2004;Stoger et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

“…For some pharmaceutical proteins expressed in plant systems, yields have varied from 0.01% to 1% of TSP (Hood et al, 2002), and have even been as low as 0.0001% of TSP . Thus, one of the key challenges for recombinant protein production in transgenic plants is the employment of effective strategies to enhance expression levels, which is a requirement for economic effi ciency (Hood et al, 2002;Fischer et al, 2004;Stoger et al, 2005). Different organisms use synonymous codons with different preferences, and the codons in the target gene can be altered to adapt codon usage of host and subsequently improve heterologous protein expression.…”

Section: Discussionmentioning

confidence: 99%

High-level expression of modified gene encoding human adiponectin in transgenic rice

2011

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Adiponectin is a polypeptide specifi cally secreted from human adipocytes, and its defi ciency is closely linked to increased obesity and type II diabetes. There is an urgent demand for large-scale production of human adiponectin for pharmaceutical applications. Here, we report that we have successfully obtained a high-level of expression of modifi ed genes encoding human adiponectin in transgenic rice. The 735 bp cDNA of the native human sequence was adopted to rice codon usage, fused to the translation initiation sequence in the N terminus and to the KDEL signal sequence in the C terminus. An amplifi cation promoting sequence acting as an enhancer of transcription was also introduced to enhance gene expression. The presence of the transgene and mRNA transcripts was confi rmed by PCR, Southern blot and RT-PCR. Western blot analysis revealed that a protein of approximately 30 kDa was produced in rice leaves. ELISA analysis was used to determine the amount of recombinant adiponectin in transformants with the modifi ed gene in up to 0.32% of total soluble leaf protein. Our results establish the feasibility of high-level expression of recombinant human adiponectin in transgenic rice.

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“…ER, endoplasmic reticulum; G, Golgi; PSV, protein storage vacuole; OB, oil body; C, chloroplast; N, nucleus; PM, plasma membrane; ES, extracellular space; PVC, prevacuolar compartment. recombinant antibodies and vaccine candidates (Hood, 2002;Hood et al, 2002;Streatfield et al, 2003). Legumes, seeds of pea and soybean, with ~40% protein content, have also been used to produce recombinant proteins including the singlechain Fv fragment antibody and humanized anti-herpes simplex virus 2 monoclonal antibody under the control of seed-specific promoter (Perrin et al, 2000;Zeitlin et al, 1998).…”

Section: Seed-based Bioreactor Platformmentioning

confidence: 99%

Plant Bioreactors for Pharmaceuticals

Miao

Ding

Sun

et al. 2008

Biotechnology and Genetic Engineering Reviews

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Plant bioreactors are attractive expression systems for economic production of pharmaceuticals. Various plant expression systems or platforms have been tested with certain degrees of success over the past years. However, further development and improvement are needed for more effective plant bioreactors. In this review we first summarize recent progress in various plant bioreactor expression systems and then focus on discussing protein compartmentation to unique organelles and various strategies for developing better plant bioreactors.

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Monoclonal antibody manufacturing in transgenic plants — myths and realities

Cited by 147 publications

References 10 publications

Cost-effective production of a vaginal protein microbicide to prevent HIV transmission

Cost-effective production of a vaginal protein microbicide to prevent HIV transmission

High-level expression of modified gene encoding human adiponectin in transgenic rice

Plant Bioreactors for Pharmaceuticals

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