Improving containment strategies in biopharming

Abstract

SummaryThis review examines the challenges of segregating biopharmed crops expressing pharmaceutical or veterinary agents from mainstream crops, particularly those destined for food or feed use. The strategy of using major food crops as production vehicles for the expression of pharmaceutical or veterinary agents is critically analysed in the light of several recent episodes of contamination of the human food chain by non-approved crop varieties.Commercially viable strategies to limit or avoid biopharming intrusion into the human food chain require the more rigorous segregation of food and non-food varieties of the same crop species via a range of either physical or biological methods. Even more secure segregation is possible by the use of non-food crops, non-crop plants or in vitro plant cultures as production platforms for biopharming. Such platforms already under development range from outdoor-grown Nicotiana spp. to glasshouse-grown Arabidopsis , lotus and moss. Amongst the more effective methods for biocontainment are the plastid expression of transgenes, inducible and transient expression systems, and physical containment of plants or cell cultures. In the current atmosphere of heightened concerns over food safety and biosecurity, the future of biopharming may be largely determined by the extent to which the sector is able to maintain public confidence via a more considered approach to containment and security of its plant production systems.

Plant Bioreactors for Pharmaceuticals

“…Upon chloroplast transformation with high copies of target gene stably integrated into the chloroplast genome, transgenic plants can accumulate recombinant proteins as high as 46% of the total leaf proteins (Arlen et al, 2007;De Cosa et al, 2001). Benefiting from the prokaryotic organization of the chloroplast genome (Arlen et al, 2007;Murphy, 2007;Svab et al, 1990), nearly no gene silencing has been observed in chloroplast bioreactor even when the accumulation of transcripts is 169 times higher in chloroplast than that in nuclear (Lee et al, 2003). In addition, the chloroplast genome can be precisely manipulated because of its small size, in which exogenous genes can be site-specifically integrated into the chloroplast genome via homologous recombination using a DNA sequence derived from the chloroplast genome (Daniell et al, 1998;Sidorov et al, 1999).…”

Evaluating biological containment strategies for pollen-mediated gene flow

“…The cultivation of transplastomic GM cultivars revealed some disadvantages in respect to containment: Although maternal inheritance is widely assumed to be the general rule in most angiosperms, rare pollen-mediated gene transfer has been detected in a number of cases (Murphy, 2007). Rare, but possible, transmission of plastid DNA via pollen (Cummins, 1998;Lu, 2003;Wang et al, 2004), even with very low levels of paternal gene transfer, may be sufficient for the escape and spread of a transgene (Haygood et al, 2004).…”

“…Plastid transformation has been achieved in many important crops, including tobacco, soybean, potato, tomato, cotton, as well in minor species, such as lettuce, petunia and Lesquerella fendleri (Brassicaceae, cultivated for oil production) and in non-crop systems, such as the alga Clamydomonas reinhardtii (Murphy, 2007). The cultivation of transplastomic GM cultivars revealed some disadvantages in respect to containment: Although maternal inheritance is widely assumed to be the general rule in most angiosperms, rare pollen-mediated gene transfer has been detected in a number of cases (Murphy, 2007).…”

“…The containment level may need to be higher for safety purposes, while much lower containment levels may be sufficient to reach coexistence goals. A wide variety of biological containment strategies for pollen-mediated gene flow have been proposed (Bock and Timmis, 2008;Daniell, 2002;Gressel and Al-Ahmad, 2005;Murphy, 2007), either naturally occurring or engineered, such as plastid transformation, cleistogamy, male sterility, complete sterility by non-flowering, transgene excision or incompatible genomes. It should be noted here that the European Commission funded a Specific Targeted Research or Innovation Project in the Sixth Framework Programme to develop efficient and stable biological containment systems for GM plants (de Maagd and Boutilier, 2009).…”

Transplastomic plants for innovations in agriculture. A review

“…There are a number of biological, chemical, and physical methods and their combinations to provide a high level of containment for such biopharmed plants. These measures include transplastomics itself (see Section 5.1), alternative production in non-food/non-feed crops or even non-crop plants, and inducible or transient expression systems (reviewed in Murphy 2007).…”