Maite Sabalza

Promoter diversity in multigene transformation

Multigene transformation (MGT) is becoming routine in plant biotechnology as researchers seek to generate more complex and ambitious phenotypes in transgenic plants. Every nuclear transgene requires its own promoter, so when coordinated expression is required, the introduction of multiple genes leads inevitably to two opposing strategies: different promoters may be used for each transgene, or the same promoter may be used over and over again. In the former case, there may be a shortage of different promoters with matching activities, but repetitious promoter use may in some cases have a negative impact on transgene stability and expression. Using illustrative case studies, we discuss promoter deployment strategies in transgenic plants that increase the likelihood of successful and stable multiple transgene expression.

The contribution of transgenic plants to better health through improved nutrition: opportunities and constraints.

Malnutrition is a prevalent and entrenched global socioeconomic challenge that reflects the combined impact of poverty, poor access to food, inefficient food distribution infrastructure, and an over-reliance on subsistence mono-agriculture. The dependence on staple cereals lacking many essential nutrients means that malnutrition is endemic in developing countries. Most individuals lack diverse diets and are therefore exposed to nutrient deficiencies. Plant biotechnology could play a major role in combating malnutrition through the engineering of nutritionally enhanced crops. In this article, we discuss different approaches that can enhance the nutritional content of staple crops by genetic engineering (GE) as well as the functionality and safety assessments required before nutritionally enhanced GE crops can be deployed in the field. We also consider major constraints that hinder the adoption of GE technology at different levels and suggest policies that could be adopted to accelerate the deployment of nutritionally enhanced GE crops within a multicomponent strategy to combat malnutrition.

The potential impact of plant biotechnology on the Millennium Development Goals

The eight Millennium Development Goals (MDGs) are international development targets for the year 2015 that aim to achieve relative improvements in the standards of health, socioeconomic status and education in the world’s poorest countries. Many of the challenges addressed by the MDGs reflect the direct or indirect consequences of subsistence agriculture in the developing world, and hence, plant biotechnology has an important role to play in helping to achieve MDG targets. In this opinion article, we discuss each of the MDGs in turn, provide examples to show how plant biotechnology may be able to accelerate progress towards the stated MDG objectives, and offer our opinion on the likelihood of such technology being implemented. In combination with other strategies, plant biotechnology can make a contribution towards sustainable development in the future although the extent to which progress can be made in today’s political climate depends on how we deal with current barriers to adoption.

High-value products from transgenic maize

Maize (also known as corn) is a domesticated cereal grain that has been grown as food and animal feed for tens of thousands of years. It is currently the most widely grown crop in the world, and is used not only for food/feed but also to produce ethanol, industrial starches and oils. Maize is now at the beginning of a new agricultural revolution, where the grains are used as factories to synthesize high-value molecules. In this article we look at the diversity of high-value products from maize, recent technological advances in the field and the emerging regulatory framework that governs how transgenic maize plants and their products are grown, used and traded.

Paradoxical EU agricultural policies on genetically engineered crops

European Union (EU) agricultural policy has been developed in the pursuit of laudable goals such as a competitive economy and regulatory harmony across the union. However, what has emerged is a fragmented, contradictory, and unworkable legislative framework that threatens economic disaster. In this review, we present case studies highlighting differences in the regulations applied to foods grown in EU countries and identical imported products, which show that the EU is undermining its own competitiveness in the agricultural sector, damaging both the EU and its humanitarian activities in the developing world. We recommend the adoption of rational, science-based principles for the harmonization of agricultural policies to prevent economic decline and lower standards of living across the continent.

Recombinant plant-derived pharmaceutical proteins: current technical and economic bottlenecks.

Molecular pharming is a cost-effective platform for the production of recombinant proteins in plants. Although the biopharmaceutical industry still relies on a small number of standardized fermentation-based technologies for the production of recombinant proteins there is now a greater awareness of the advantages of molecular pharming particularly in niche markets. Here we discuss some of the technical, economic and regulatory barriers that constrain the clinical development and commercialization of plant-derived pharmaceutical proteins. We also discuss strategies to increase productivity and product quality/homogeneity. The advantages of whole plants should be welcomed by the industry because this will help to reduce the cost of goods and therefore expand the biopharmaceutical market into untapped sectors.

EU legitimizes GM crop exclusion zones

315 To the Editor: On July 13, 2010, the European Commission (EC) officially proposed to give member states the freedom to veto the cultivation of genetically modified (GM) crops on their own territory without having to provide any scientific evidence relating to new risks1. The objective of the legislation is ostensibly to make individual member states responsible for their own policy on GM crops, and therefore to speed up pending authorizations by removing the ability of those member states to veto approval throughout the European Union by avoiding a qualified majority (Fig. 1). However, we argue that the opt-out will have exactly the opposite effect to that intended, allowing the creation of arbitrary GM-free zones in Europe that will cause untold damage to the EU economy and its global scientific standing. The removal of any need for scientific justification in decisions concerning GM crops effectively serves to legalize the currently illegal practice in which individual member states arbitrarily declare GM-free zones within their borders, or ban GM crops altogether2. The only GM crops currently grown in Europe are the pest-resistant maize variety MON810 and the Amflora potato variety engineered to produce modified starch. Both are banned in Austria, Hungary and Luxembourg, and the MON810 event is also banned in France, Greece and Germany (Table 1). Poland is currently drawing up legislation to ban all GM seeds, and other member states are considering similar proposals. Although these existing and proposed bans are technically in breach of EU regulations, at least those member states implementing a ban have to make some sort of effort to justify their decision on scientific grounds, even if the evidence used in such cases is dubious (the ‘safeguard clause’). When the legal amendment enters into force, member states will be free to restrict or prohibit the cultivation of all or particular GM crops within their territory, including crops that have already been authorized for cultivation under Directive 2001/18/EC and Regulation EC 1829/2003, and will be able to do so without explanation. This places the future of GM agriculture in Europe at the whim of politicians who may feel compelled to act in response to the media or activist propaganda. EU policy on agriculture has evolved over the past 50 years as the continent has moved from the position of a net importer struggling to feed its population at the end of a devastating war, to today’s near trade parity with the rest of the world. Even so, the EU is still a net importer of agricultural raw materials and 55% of imports come from ten countries, with Brazil, the United States and Argentina ranking in the top three positions3. The same three countries also happen to be the world’s largest adopters of GM technology, with the United States planting 64 million hectares of transgenic crops in 2009 and both Brazil and Argentina planting just over 21 million hectares4. Paradoxically, although the proposed amendment will allow member states to adopt measures against the cultivation of GM crops, they will not be allowed to adopt measures prohibiting the import or marketing in the European Union of authorized GM products from elsewhere, which means that EU markets are likely to be flooded with imported GM products that could just as easily be homegrown. However, the import of GM products is also heavily regulated, as is particularly apparent in the EU’s treatment of imported maize and soybean from the United States and elsewhere, which has a substantial knock-on effect on animal agriculture. In this context, the European Union is deficient in feed protein and is ultimately dependent on soybean meal imports. However, imports have declined considerably (from

Trehalose, an mTOR-Independent Inducer of Autophagy, Inhibits Human Cytomegalovirus Infection in Multiple Cell Types

2.8 billion in 1997 to

Seeds as a Production System for Molecular Pharming Applications: Status and Prospects

1.9 billion in 2008)5, predominantly because of the complex and onerous process for approving imported GM products, which is administrated at the member state level after the European Food Safety Authority (Parma, Italy) has issued opinions declaring that products are safe. The United States Department of Agriculture states that GM events take on average 15 months to approve in the EU legitimizes GM crop exclusion zones

Can the world afford to ignore biotechnology solutions that address food insecurity

ABSTRACT Human cytomegalovirus (HCMV) is the major viral cause of birth defects and a serious problem in immunocompromised individuals and has been associated with atherosclerosis. Previous studies have shown that the induction of autophagy can inhibit the replication of several different types of DNA and RNA viruses. The goal of the work presented here was to determine whether constitutive activation of autophagy would also block replication of HCMV. Most prior studies have used agents that induce autophagy via inhibition of the mTOR pathway. However, since HCMV infection alters the sensitivity of mTOR kinase-containing complexes to inhibitors, we sought an alternative method of inducing autophagy. We chose to use trehalose, a nontoxic naturally occurring disaccharide that is found in plants, insects, microorganisms, and invertebrates but not in mammals and that induces autophagy by an mTOR-independent mechanism. Given the many different cell targets of HCMV, we proceeded to determine whether trehalose would inhibit HCMV infection in human fibroblasts, aortic artery endothelial cells, and neural cells derived from human embryonic stem cells. We found that in all of these cell types, trehalose induces autophagy and inhibits HCMV gene expression and production of cell-free virus. Treatment of HCMV-infected neural cells with trehalose also inhibited production of cell-associated virus and partially blocked the reduction in neurite growth and cytomegaly. These results suggest that activation of autophagy by the natural sugar trehalose or other safe mTOR-independent agents might provide a novel therapeutic approach for treating HCMV disease. IMPORTANCE HCMV infects multiple cell types in vivo, establishes lifelong persistence in the host, and can cause serious health problems for fetuses and immunocompromised individuals. HCMV, like all other persistent pathogens, has to finely tune its interplay with the host cellular machinery to replicate efficiently and evade detection by the immune system. In this study, we investigated whether modulation of autophagy, a host pathway necessary for the recycling of nutrients and removal of protein aggregates, misfolded proteins, and pathogens, could be used to target HCMV. We found that autophagy could be significantly increased by treatment with the nontoxic, natural disaccharide trehalose. Importantly, trehalose had a profound inhibitory effect on viral gene expression and strongly impaired viral spread. These data constitute a proof-of-concept for the use of natural products targeting host pathways rather than the virus itself, thus reducing the risk of the development of resistance to treatment.