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Defensive applications of gene transfer technology in the face of bioterrorism: DNA-based vaccines and immune targeting.

Gene transfer involves the introduction of an engineered gene into a person's cells with the expectation that the protein expressed from the gene will produce a therapeutic benefit. Strategies based on this principle have led to the approval of > 600 clinical trials and enrollment of approximately 3500 subjects worldwide in attempts to treat diseases ranging from cancer to AIDS to cystic fibrosis. While gene therapy has met with limited success and still has many hurdles to overcome before it sees wide application, it may be useful as a defensive strategy against bioterrorism agents including infectious microbes and toxins. Although many defensive strategies are possible, immunological strategies are currently the most developed and are being actively applied to the development of strategies against several of the most virulent potential bio-weapons. While most of these strategies are not yet ready for human application, DNA-based vaccines appear to be among the most promising in the fight against bioterrorism.

Animals↗

Nuclear transfer technology in mammalian cloning.

The past several years have witnessed remarkable progress in mammalian cloning using nuclear transfer (NT). Until 1997 and the announcement of the successful cloning of sheep from adult mammary gland or fetal fibroblast cells, our working assumption was that cloning by NT could only be accomplished with relatively undifferentiated embryonic cells. Indeed, live offspring were first produced by NT over 15 years ago from totipotent, embryonic blastomeres derived from early cleavage-stage embryos. However, once begun, the progression to somatic cell cloning or NT employing differentiated cells as the source of donor nuclei was meteoric, initially involving differentiated embryonic cell cultures in sheep in 1996 and quickly thereafter, fetal or adult somatic cells in sheep, cow, mouse, goat, and pig. Several recent reviews provide a background for and discussion of these successes. Here we will focus on the potential uses of reproductive cloning along with recent activities in the field and a discussion concerning current interests in human reproductive and therapeutic cloning.

Animal Husbandry↗

Evaluation of critical points in technology transfer of cryopreservation protocols to international plant conservation laboratories.

Cryopreservation of plant tissues in liquid nitrogen is now used for long-term conservation of vegetatively-propagated crops. Development of standard techniques for cryopreservation is important to the international plant-conservation community for successful implementation of storage protocols in diverse and internationally dispersed laboratories. Evaluation of the critical points of each preservation technique will greatly assist in developing and validating internationally-used cryopreservation protocols. The goals of this project were to assess critical points of two major cryopreservation techniques (PVS2 vitrification and encapsulation dehydration) during their transfer to international laboratories; analyze post-storage viability for each technique and location; and develop recommendations based on the assessments and data from the participating laboratories. Investigators from Germany, Kazakhstan, Poland and UK participated in a 2-week training workshop in cryopreservation methods after which the techniques were tested in the home laboratories of the participants. After one-year site visits by the technology trainers identified critical points in the protocols. Critical points were identified as 1) Cryogenic (cryoprotection, LN exposure, rewarming); 2) Non-cryogenic (plant health status, pre- and post-storage culture); 3) Operational (skills transfer, training, interpretation of procedures); 4) Facility (growth room, ambient conditions, media preparation, equipment). The most critical factors in all laboratories were culture health, operator skills and experience, and clarification of the technical details of the procedures. Final results showed that correction of critical factors improved the post-storage recovery in all the laboratories.

Conservation of Natural Resources↗

Commercial feasibility of embryo transfer technology: a case study.

The owner of a 500-cow Holstein herd requested economic assessment of his embryo transfer program. Actual net economic benefit was determined from marginal cost and present value of lifetime milk predicted from first lactations of 24 cows produced by embryo transfer compared with those of their 51 contemporaries sired by artificial insemination. Actual average pregnancy rate was 60% by embryo transfer or AI. An average of 5.5 transferable embryos was obtained per collection, which produced 1.37 cows in first lactation. Additional milk from embryo transfer cows was from more intensive selection of sires. Additional milk from the donor cows did not differ from zero. Actual marginal cost of a replacement by embryo transfer was +215, but it would have been +200 with same +25/unit semen price as contemporaries. If donors had been from the elite 5% for transmitting ability in milk, present value of gain in milk (5% real interest rate) ignoring additional feed costs would have been less than the cost of embryo transfer. For management and costs similar to this case, embryo transfer is not economically justified for producers earning income primarily from the sale of milk.

Animal Husbandry↗

Afterword: bottom-line status report: CAN current trends in membrane gas transfer technology lead to an implantable intrathoracic artificial lung?

For at least 170 years, attempts have been made to alleviate inadequate gas exchange of patients with respiratory failure. Major milestones in the struggle to assist failing natural lungs to achieve adequate blood gas exchange include utilization of oxygen inhalation therapy, mechanical ventilatory assistance, and development of both extracorporeal and intracorporeal mechanical blood gas exchangers. Current state-of-the-art technology related to mechanical membrane blood gas exchangers has produced highly efficient gas transfer membranes and designs capable of replacing all the gas transfer functions of the natural lungs by a mechanical oxygenator-CO2 remover that can fit into a unilateral thoracic cavity. The possibility thus exists of moving extracorporeal mechanical blood oxygenators into the body as an implantable intracorporeal artificial lung. Problems impeding the development of an implantable, intrathoracic artificial lung have been identified, and at least partially successful attempts to solve them have been reported. The conclusion drawn is that the appropriate answer to the question posed in the title of this communication is affirmative. Reasons for this conclusion include the persistent widespread major need for better relief from respiratory failure, the advanced state-of-the-art of mechanical blood gas exchanger technology, and the incompletely tapped ingenuity of the human mind.

Artificial Organs↗

Technology transfer.

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Developing Countries↗

Binary transformation systems based on 'shooter' mutants of Agrobacterium tumefaciens: a simple, efficient and universal gene transfer technology that permits marker gene elimination.

A simple transformation procedure with a positive selection scheme using the expression of the isopentenyl transferase ( ipt) gene of transfer DNA (T-DNA) 'shooter' mutants of Agrobacterium tumefaciens was elaborated. After comparing several 'shooter' mutants we found that particular strains frequently produced phenotypically normal shoots after co-culturing with tobacco leaf explants. Shoots selected for normal phenotype showed apical dominance and could be rooted with the same efficiency as non-transformed shoots. When binary vectors were introduced into these strains, stably integrated binary vector T-DNA sequences were found in some regenerants, which were produced under non-selective conditions on growth-regulator-free medium. Such phenotypically normal transformants typically lacked a stably integrated ipt gene. Normal looking shoots could also be produced in tomato, muskmelon and sweet pepper.

Agrobacterium tumefaciens↗

Technology transfer in the diagnostics industry.

Initiatives are underway to increase links between researchers and inventors working in the diagnostics sector and companies ready to commercialize the new technologies. This article describes the formation and aims of two groups working in this area, and reports on a review that has been made of the market requirements and opportunities for advanced sensors in the health care sector. The medical sensors market is predicted to expand during the next few years and the best opportunities for their development are outlined.

Diagnosis↗

Moving out. Technology transfer from hospitals to outpatient facilities.

The Temple Radiology Group opened on July 1, 1977 in the Temple Medical Center. The initial 10-room, full-service department has grown with new technology into approximately 25 rooms. The original four-room Temple surgery center has grown to 10 rooms. Additional support facilities that have evolved include: 1) a computer company; 2) physical therapy for orthopedic, neurological and cardiac patients; 3) a brain trauma center; 4) a collection agency; and most recently, 5) a 100-bed medical hotel.

Diagnostic Imaging↗

Technology transfer: the importance of people.

Major advances in molecular and cell biology lead a modern biological revolution. The question we must ask concerns whether New Zealand will capture the advantages of new knowledge and technology in basic medical research, and in clinical and social medicine. The problems of applying new science to medicine require a new look at forward planning and research goals.

Biotechnology↗