Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants

Daniell, Henry; Streatfield, Stephen J.; Wycoff, Keith L.

doi:10.1016/s1360-1385(01)01922-7

Cited by 665 publications

(435 citation statements)

References 54 publications

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“…Although pharmaceutical proteins have been synthesized from plant nuclear transgenes, expression levels (particularly of human proteins) are generally disappointingly low [38]. Chloroplasts, with their highly polyploid genomes offer an ideal compartment for overproduction of foreign proteins.…”

Section: Engineering the Chloroplast Genome To Overproduce Biopharmacmentioning

confidence: 99%

Milestones in chloroplast genetic engineering: an environmentally friendly era in biotechnology

Daniell

Khan

Allison

2002

Trends in Plant Science

324

153

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Chloroplast genomes defied the laws of Mendelian inheritance at the dawn of plant genetics, and continue to defy the mainstream approach to biotechnology, leading the field in an environmentally friendly direction. Recent success in engineering the chloroplast genome for resistance to herbicides, insects, disease and drought, and for production of biopharmaceuticals, has opened the door to a new era in biotechnology. The successful engineering of tomato chromoplasts for high-level transgene expression in fruits, coupled to hyper-expression of vaccine antigens, and the use of plant-derived antibiotic-free selectable markers, augur well for oral delivery of edible vaccines and biopharmaceuticals that are currently beyond the reach of those who need them most.Chloroplast transformation is an environmentally friendly approach to plant genetic engineering that minimizes out-crossing of transgenes to related weeds or crops [1,2] and reduces the potential toxicity of transgenic pollen to non-target insects [3]. Because the plastid genome is highly polyploid, transformation of chloroplasts permits the introduction of thousands of copies of foreign genes per plant cell, and generates extraordinarily high levels of foreign protein [3]. Chloroplast transformation vectors use two targeting sequences that flank the foreign genes and insert them, through homologous recombination, at a precise, predetermined location in the organelle genome (Fig. 1). This results in uniform transgene expression among transgenic lines and eliminates the 'position effect' often observed in nuclear transgenic plants. Gene silencing, frequently observed in nuclear transgenic plants, has not been observed in genetically engineered chloroplasts. The ability to express foreign proteins at high levels in chloroplasts and chromoplasts, and to engineer foreign genes without the use of antibiotic resistant genes [4,5],make this compartment ideal for the development of edible vaccines [6]. Moreover, the ability of chloroplasts to form disulfide bonds and to fold human proteins has opened the door to high-level production of biopharmaceuticals in plants [7]. Furthermore, foreign proteins observed to be toxic in the cytosol are non-toxic when accumulated within transgenic chloroplasts [6,8]. Chloroplast and nuclear genetic engineering are compared in Table 1.

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Section: Engineering the Chloroplast Genome To Overproduce Biopharmacmentioning

confidence: 99%

Milestones in chloroplast genetic engineering: an environmentally friendly era in biotechnology

Daniell

Khan

Allison

2002

Trends in Plant Science

324

153

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“…Animal-, plant-, and insect cell cultures have become significant tools in the production of proteins and biopharmaceuticals for applications involving humans [Baldi et al, 2007, Daniell et al, 2001, Walsh, 2006, Wurm, 2004. Animal cell lines, such as Chinese hamster ovary (CHO), hybridoma, human embryo kidney (HEK) or baby hamster kidney (BHK) cells are commonly used as production cells [Baldi et al, 2007, Butler, 2005, Walsh, 2006, Wurm, 2004.…”

Section: Introductionmentioning

confidence: 99%

Process control in cell culture technology using dielectric spectroscopy

Justice¹,

Brix

Freimark³

et al. 2011

Biotechnology Advances

107

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“…Plants are becoming a common platform for production of recombinant proteins such as industrial enzymes and pharmaceuticals (Daniell et al 2001;Kusnadi et al 1997). A production system using recombinant plants potentially offers great advantages over those based on microorganisms or animal cells when foreign gene products are produced, because it can be applied to traditional agricultural system at low cost (Twyman et al 2003).…”

Section: Introductionmentioning

confidence: 99%

Acquired resistance to the rice blast in transgenic rice accumulating the antimicrobial peptide thanatin

et al. 2009

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Thanatin is an antimicrobial peptide with a strong and wide-ranging antimicrobial spectrum, including certain species of fungi and Gram-negative and -positive bacteria. To evaluate the application of thanatin to the generation of disease-resistant plants, we introduced a synthetic thanatin gene into rice. Several transformants that expressed the introduced gene showed significant level of antimicrobial activity. The substances showing antimicrobial activity were partially purified from these transformants and their properties were determined. The molecule with characteristics similar to those of native thanatin on the elution pattern in HPLC analysis had an identical molecular mass to that of native molecule. It should also be noted that the transformant acquired a sufficient level of resistance to the rice blast fungus, Magnaporthe oryzae, presumably due to the repressive activity of thanatin to its initial stage of infection. This result demonstrates that thanatin has antifungal activity for M. oryzae and that the introduction of the thanatin gene into rice is effective in generating a plant resistant to rice blast disease.

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Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants

Cited by 665 publications

References 54 publications

Milestones in chloroplast genetic engineering: an environmentally friendly era in biotechnology

Milestones in chloroplast genetic engineering: an environmentally friendly era in biotechnology

Process control in cell culture technology using dielectric spectroscopy

Acquired resistance to the rice blast in transgenic rice accumulating the antimicrobial peptide thanatin

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