Increasingly, basic, translational, and clinical research has become more collaborative, resulting in multi-institutional studies that involve common approaches to a central question. For multi-institutional projects that involve recombinant or synthetic nucleic acids, Institutional Biosafety Committee (IBC) review is generally required at each separate site. Duplicative review may result in both administrative costs and delays, without evidence of increased safety or protections, and investigator frustration. To address these inefficiencies, IBC leaders drafted a collaborative IBC Reliance Authorization Agreement. The Agreement allows one or more institutions to cede IBC review to a reviewing IBC that accepts the responsibility. The ability to cede IBC review, and the ability to rely on one decision on behalf of all collaborating institutions for a given protocol, removes delays in approval of multi-center protocols, and collaborating principal investigators are able to focus on research rather than administrative tasks. In the process, we found promotion of this collaborative model led to stronger connections among institutions and among IBC members. The requirement for IBC member representation from the local community, however, limits its broader dissemination; we make several recommendations to mitigate this challenge.

There is a worldwide consensus that the production of food, biomolecules and bioenergy should be sustainably intensified within the next decades. To achieve these goals will depend on the intensification of current practices in agricultural systems fused with a wider understanding and acceptance of genomics, metabolomics, synthetic biology and metabolic engineering. However, genetically modified-derived crops, including commodities and non-commodities, may contribute to establishing a new parameter in the agricultural, pharmaceutical and industrial sectors. Seeds will also play an important role in allowing large-scale production of innovative molecules prospected from biodiversity.

This target article describes the current state of global gene replacement in the brain using viral vectors and assesses possible solutions to some of the many problems inherent in gene therapy of the central nervous system (CNS). Gene replacement therapy in the CNS is a potential means of producing a stable expression of normal human proteins in deficient cells and thus curing certain genetically inherited enzyme deficiencies and metabolic diseases as well as cancers. The two major issues to be addressed in CNS gene replacement are the delivery of genetic material to the brain and the expression of recombinant genetic material in target cells within the CNS. Focal inoculation of recombinant virions or other genetic vectors has limitations in global CNS disease. A new approach is the blood-brain barrier (BBB) disruption technique developed in this laboratory, in which hypertonic mannitol transiently shrinks the BBB endothelium, allowing passage of high molecular weight compounds and even viruses. Gene therapy of the CNS will require a viral vector system that allows long-term, nontoxic gene expression in neurons or glial cells. Retroviral vectors have limitations in CNS gene replacement, although they are suitable for expressing recombinant genes in intracerebral grafts, or toxic genes in brain tumors. Using mutant neurotropic viruses with reduced neurotoxicity (such as defective herpes simplex virus type I [HSV-1], the HSV-1 amplicon vector system we have developed, or adenovirus mutants) has potential for direct treatment of neurons. Injecting these vectors into rodent brains can lead to stable expression of foreign genetic material in postmitotic neuronal cells. We discuss our BBB disruption delivery technique, our defective HSV-1 amplicon vector system, and our feline model for the neuronal lysosomal storage disorder Gm2-gangliosidosis (Sandhoff disease), which may prove to be a useful model system for CNS gene therapy.

The presence of recombinant DNA in soil cultivated with white poplars (Populus alba L.) expressing either the bar transgene for herbicide tolerance or the StSy transgene for resveratrol production, respectively, was investigated in a greenhouse over a 20-month period. The bar trial included the transgenic lines 5P56 and 6EA22P56 and the untransformed line, while the StSy trial was established with the transgenic lines 5EAC1 and 12EAC1 and with the untransformed line. All the transgenic poplars harbored the nptII marker gene. Plantlets were cultivated in pots, and soil samples were mixed in order to obtain composite pools which were used for molecular analyses. The 35SCaMV-bar (1504 bp), 35SCaMV-StSy (1403 bp) and NosP-nptII (1188 bp) sequences were detected in total DNA extracted from soil samples taken at different times after planting, using PCR/Southern blot hybridization. Microcosm experiments, carried out to assess the effects of temperature and DNA purity on transgene persistence, revealed only a partial correlation between the intensity of hybridization signals and the parameters tested.

Studies on genetically modified (GM) feedstuffs for poultry (and other livestock species) have not added any substance to public concerns in Europe about their safety for human or bird health. The compositions of maize lines engineered for insect resistance (Bt-maize) or herbicide tolerance (glyphosate) and herbicidetolerant soybean have all proved to be essentially indistinguishable from their conventional counterparts. Consequently, and not surprisingly, comparative feeding studies with broilers and layers in which conventional maize (50 to 78%) or soybeans (27%) were replaced in feeds by transgenic varieties, also have failed to show differences of any significance in production parameters. These data indicate that feeding studies with target livestock species contribute very little to the safety assessment of crops engineered for input traits that have little or no detectable effect on chemical composition. However, comparative growth studies made with broiler chicks, particularly sensitive to any change in nutrient supply or the presence of toxic elements in their feed, can be used to screen for any unintended adverse consequence of the recombinant event not detected by compositional analysis. This does, however, depend on whether the GM plant can be matched to a parental line or another suitable control and its suitability for inclusion in broiler diets. The discovery that DNA fragments from the digestive tract can be found in the tissues of animals evoked interest in the fate of ingested transgenes. Plant DNA derived from feed has been detected in the muscle, liver, spleen and kidneys of broilers and layers, although not in eggs. However, no fragments of transgenic DNA or its expressed protein have been found to date in poultry meat or eggs or in any other animal tissues examined.

The prospect of the deliberate environmental release of genetically manipulated microorganisms has given rise to a great deal of polemic. Amongst the rational scientific concerns are those concerned with the fate of the released bacteria, the fate of the recombinant genes that they carry, the selective pressures acting upon them in different environmental situations and the long term effects on the environment and human health. All recombinant DNA is carried by vectors (plasmids, transposons or bacteriophage or remnants of these). Thus the way in which recombinant constructions are made may itself lead to potential biosafety concerns, irrespective of the host bacterium and the recombinant DNA fragment of primary interest. The purpose of the present review is to assess progress in improved vector design aimed at eliminating risks due to the way recombinant vectors are constructed. Improved vector constructions include the avoidance of the use, or removal, of antibiotic resistance genes, the use of defective transposons rather than plasmids in order to reduce horizontal transfer and the development of conditionally lethal suicide systems. More recently, new site-specific recombination systems have permitted transposon vectors to be manipulated following strain construction, but before environmental release, so that virtually all recombinant DNA not directly involved in the release experiment is eliminated. Such bacteria are thus pseudo-wild type in that they contain no heterologous DNA other than the genes of interest.

Live attenuated strains of Salmonella spp. make excellent vaccines against salmonellosis in experimental animals, eliciting a cell-mediated, mucosal and humoral immune response. In addition, new recombinant DNA technology permits the expression in Salmonella strains of protective antigens from unrelated bacterial, viral or parasitic pathogens. Exciting possibilities exist for a single live vaccine which could provide protection against two or more infectious agents. Recently, attenuated strains of the chicken pathogen Salmonella gallinarum have been considered as the basis of a live multivalent poultry vaccine and work is progressing on the expression of coccidial and herpes viral antigens in strains of Salmonella.