Optimizing product quality in molecular farming

Schiermeyer, Andreas

doi:10.1016/j.copbio.2019.08.012

“…The knockout of protease genes by genome editing is a more effective approach. Different proteases can contribute to the degradation of a target protein by attacking different regions, so multiplex editing would be required to remove all relevant proteases (Schiermeyer 2020). In such cases, the extraordinary versatility of the CRISPR/Cas9 system is a great advantage, particularly its compatibility with multiplex editing.…”

Section: Modulating Endogenous Protease Activitymentioning

confidence: 99%

Targeted genome editing of plants and plant cells for biomanufacturing

Buyel

¹

,

Stöger

²

,

Bortesi

³

2021

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Plants have provided humans with useful products since antiquity, but in the last 30 years they have also been developed as production platforms for small molecules and recombinant proteins. This initially niche area has blossomed with the growth of the global bioeconomy, and now includes chemical building blocks, polymers and renewable energy. All these applications can be described as “plant molecular farming” (PMF). Despite its potential to increase the sustainability of biologics manufacturing, PMF has yet to be embraced broadly by industry. This reflects a combination of regulatory uncertainty, limited information on process cost structures, and the absence of trained staff and suitable manufacturing capacity. However, the limited adaptation of plants and plant cells to the requirements of industry-scale manufacturing is an equally important hurdle. For example, the targeted genetic manipulation of yeast has been common practice since the 1980s, whereas reliable site-directed mutagenesis in most plants has only become available with the advent of CRISPR/Cas9 and similar genome editing technologies since around 2010. Here we summarize the applications of new genetic engineering technologies to improve plants as biomanufacturing platforms. We start by identifying current bottlenecks in manufacturing, then illustrate the progress that has already been made and discuss the potential for improvement at the molecular, cellular and organism levels. We discuss the effects of metabolic optimization, adaptation of the endomembrane system, modified glycosylation profiles, programmable growth and senescence, protease inactivation, and the expression of enzymes that promote biodegradation. We outline strategies to achieve these modifications by targeted gene modification, considering case-by-case examples of individual improvements and the combined modifications needed to generate a new general-purpose “chassis” for PMF.

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“…Plant molecular pharming (PMP) is based on the ability of plants to express different genes for preventive and therapeutic purposes and it holds promise [11]. The production and commercialization of recombinant proteins and pharmaceutical compounds from plants has been optimized and relatively successful over the past few years [11][12][13][14][15]. The concept of PMP as a biofactory was demonstrated earlier on [16] and presents many advantages over conventional systems that rely on bacteria, yeast, insect and animal cell cultures for pharmaceutical products [13].…”

Section: Plant-based Biofactoriesmentioning

confidence: 99%

Plant-made HIV vaccines and potential candidates

Trémouillaux-Guiller

¹

,

Moustafa²,

Hefferon

³

et al. 2020

Current Opinion in Biotechnology

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Millions of people around the world suffer from heavy social and health burdens related to HIV/AIDS and its associated opportunistic infections. To reduce these burdens, preventive and therapeutic vaccines are required. Effective HIV vaccines have been under investigation for several decades using different animal models. Potential plant-made HIV vaccine candidates have also gained attention in the past few years. In addition to this, broadly neutralizing antibodies produced in plants which can target conserved viral epitopes and neutralize mutating HIV strains have been identified. Numerous epitopes of glycoproteins and capsid proteins of HIV-1 are a part of HIV therapy. Here, we discuss some recent findings aiming to produce anti-HIV-1 recombinant proteins in engineered plants for AIDS prophylactics and therapeutic treatments.

show abstract

“…Plant molecular pharming (PMP) is based on the ability of plants to express different genes for preventive and therapeutic purposes and it holds promise [11]. The production and commercialization of recombinant proteins and pharmaceutical compounds from plants has been optimized and relatively successful over the past few years [11][12][13][14][15]. The concept of PMP as a biofactory was demonstrated earlier on [16] and presents many advantages over conventional systems that rely on bacteria, yeast, insect and animal cell cultures for pharmaceutical products [13].…”

Section: Plant-based Biofactoriesmentioning

confidence: 99%

Plant-made HIV vaccines and potential candidates

Tremouillaux-Guiller,

Moustafa,

Hefferon

et al. 2020

Preprint

0

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Millions of people around the world suffer from heavy social and health burdens related to HIV/AIDS and its associated opportunistic infections. To reduce these burdens, preventive and therapeutic vaccines are required. Effective HIV vaccines have been under investigation for several decades using different animal models. Potential plant-made HIV vaccine candidates have also gained attention in the past few years. In addition to this, broadly neutralizing antibodies produced in plants which can target conserved viral epitopes and neutralize mutating HIV strains have been identified. Numerous epitopes of glycoproteins and capsid proteins of HIV-1 are a part of HIV therapy. Here, we discuss some recent findings aiming to produce anti-HIV-1 recombinant proteins in engineered plants for AIDS prophylactics and therapeutic treatments.

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Optimizing product quality in molecular farming

Cited by 15 publications

References 58 publications

Targeted genome editing of plants and plant cells for biomanufacturing

Targeted genome editing of plants and plant cells for biomanufacturing

Plant-made HIV vaccines and potential candidates

Plant-made HIV vaccines and potential candidates

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