Nature Biotechnology pp 1087 - 1090

The male of the species could be superior to the female, at least when it comes to producing pharmaceutical proteins. Until now, scientists have focused on female transgenic animals, such as nanny goats and ewes, to produce protein drugs in their milk. But this approach is limited not only by the delay before female sexual maturity and the onset of first lactation, but also by the intermittent nature of lactation itself. Now, Francois Pothier and colleagues have created male transgenic mice that secrete human growth hormone into their ejaculate. They suggest that boars (male pigs), which can produce up to half a liter of semen at a time, could be similarly engineered to produce pharmaceutical proteins both cost-effectively and efficiently.

Working on the premise that semen is one of the bodyís richest and easily collected sources of protein, Pothierís team set out to produce human growth hormone (hGH) in the ejaculate of genetically engineered mice. They achieved this through the use of a DNA gene promoter sequence, P12, which is only active in male sex glands such as the seminal vesicle. By injecting fertilized mouse eggs with DNA encoding hGH linked up to the P12 DNA sequence, they showed that the hormone was secreted specifically into the semen of male animals. Gene expression analysis revealed that hGH was expressed in the seminal vesicle and the kidney, but in no other organs. Although the amount of protein in each milliliter of ejaculate (0.5 mg/ml) was less than in other transgenic systems, such as goats milk, Pothier suggests it may be possible to optimize the system to achieve higher expression. Experiments are currently under way to test the technique in boars.

Nature Biotechnology pp 1083 - 1086

Many of the more than half a million patients who undergo heart bypasses in the United States every year do not have sufficient healthy arteries to donate for the operation. Although synthetic blood vessels can be used as substitutes, they tend to clog up and cause dangerous blood clots, especially when they are small (<5--6 mm) and implanted in regions of the body where blood flow is sluggish. Now, Susan Sullivan and her colleagues have engineered small (4 mm) artificial blood vessels from collagen tubes coated with a layer of anticoagulant heparin. On implantation into rabbits, these tubes attract vascular cells so that, after three months, they resemble normal blood vessels in both their morphological structure and their responses to natural vasoconstrictive agents.

Previous attempts to engineer biosynthetic blood vessels have often relied on growing arteries from scratch using laboratory-grown vascular cells, but such vessels often rupture and clog when implanted in the body. Sullivanís group took a different approach, providing a collagen framework on to which vascular cells could grow in situ and letting the body do the work of the tissue engineer. They constructed the synthetic vessels by forming a tube of collagen (extracted from the pig small intestine), adding another thin inner layer of cow collagen, cementing the resulting two-layer tube together with a crosslinking agent, and coating the inner surface with heparin anticoagulant. When implanted into the rabbit carotid artery, the tubes withstood suturing and lasted up to three months, with no signs of immunological rejection. Whatís more, as time progressed, the tubes gradually filled up with vascular cells from adjoining blood vessels until, after three months, they resembled natural arteries, with layers of smooth muscle cells on the outside and endothelial cells on the inside. In vitro experiments of explanted tubes in the presence of bradykinin, serotonin, norepinephrine, and potassium chloride also showed that the synthetic vessels contract in response to same chemical signals that spur normal arterial contractions.

Nature Biotechnology pp 1122 - 1124

Much in the same way that adjuvants are added to vaccines to potentiate immunogenicity, scientists have engineered transgenic rice plants with a factor that boosts the effectiveness of a biopesticide against caterpillars. This factor, virus-enhancing factor, works synergistically with a biopesticide called nucleopolyhedrovirus (NPV), which when sprayed on rice plants kills infesting insects. In this issue, a team of Japanese researchers, headed by Tosihiko Hukuhara, show that the rice pest armyworm is much more susceptible to NPV when feeding on transgenic rice plants containing the virus-enhancing factor. Their approach could considerably boost the effectiveness and economics of NPV biopesticides in the field.

NPV is an important natural pathogen of several insect pests, such as cabbage looper, potato tuberworm, and armyworm caterpillars, and has therefore been promoted as potentially important biopesticide. Because NPV acts relatively slowly (4--8 days), targets only a select group of insects, and is costly to produce, scientists are searching for ways enhance its potency as an insecticide. Hukuhara and his collaborators have stably introduced the virus-enhancing factor gene from an entomopoxvirus into rice cells, generating two generations of transgenic plants that produce the factor in their leaves. When armyworm larvae were fed on rice leaves and a synthetic artificial diet containing different concentrations of NPV, approximately 40-fold less NPV was required to infect caterpillars fed on transgenic leaves than those fed on wild leaves. The authors propose that the approach might be useful for enhancing NPV susceptibility in other types of insect pests, expanding the range of current NPV biopesticides.