Editor's note: Science Scan is a quick round-up of recently published,biotechnology-related research.
As a left-handed monkey wrench for jamming the machinery ofprotein expression, antisense technology hasn't fully lived up to thepromises that heralded this genetic-code-blocking approach in theearly 1990s.
Now, in the current Proceedings of the National Academy ofSciences (PNAS), dated April 16, 1996, Gilead Sciences Inc., ofFoster City, Calif., and its research ally, Glaxo Wellcome, ofResearch Triangle Park, N.C. introduce, "A serum-resistantcytofectin [GS 2888] for cellular delivery of antisenseoligodeoxynucleotides and plasmid DNA."
The paper's senior author, Richard Wagner, is director of cellbiology at Gilead. "The discovery and use of GS 2888," he said, "hasallowed us to perform gene knockouts in cell culture, giving us theability to link disease with protein function."
He described GS 2888, a cationic liposomal vehicle, as "a proprietarypermeation enhancer for the efficient delivery of oligonucleotides andother genetic material to the inside of cells."
Expert Panel Urges Moratorium On GeneTest For Predicting Alzheimer's Disease
"A little knowledge is a dangerous thing." That in essence is the take-home message promulgated by a mixed panel of biomedical andsocial scientists, convened to judge the effects of a prognostic genetest for Alzheimer's disease (AD).
The National Institutes of Health's National Institute on Aging andthe Chicago-based Alzheimer's Association assembled the 33-member working group last October for a two-day conference toexplore "the application of APOE genotyping to the prediction anddiagnosis of AD."
Their consensus statement appears in the current issue of The Lancet,dated April 20, 1996. Its overall conclusion: "The use of APOEgenotyping to predict future risk of AD in symptom-free individualsis not recommended at this time."
APOE stands for Apolipoprotein E, a molecule best known for itsrole in cholesterol metabolism. (See BioWorld Today, March 23,1995, p. 1.) As one might expect, the liver makes apolipoproteins,but astrocytes in the brain also express APOE.
Its gene, on chromosome 19, comes in three variants: APOE2, 3 and4. A person who inherits APOE4 (heterozygotically) from one parenthas a two- to four-fold higher risk of developing AD;(homozygotically) from both parents, five to 18-fold higher.
Commercially available DNA blood tests for these APOE alleles aidphysicians in assessing their patients' chances of gettingatherosclerosis. But now that the assay offers odds of acquiringAlzheimer's disease, people are beating at their doctors' doors to betested.
In its report, the task force warned of "social harm to those who seekAPOE genotyping." Besides the test's inherent uncertainties, itconcluded, "Concerns include access to insurance . . . employment,social stigma and family dynamics."
Athena Neurosciences Inc., of S. San Francisco, holds patent rightsfrom Duke University covering APOE testing for AD diagnostics.(See BioWorld Today, Aug. 23, 1995, p. 3.)
Muscular Motor Protein Myosin Shows Surprising StructuralSimilarity To Sub-Cellular Kinesins
We now have frequent evidence that nature is not above imitatingitself. When widely differing life forms have identical stretches ofDNA in their genomes, we call that homology "conservation."
A lot of motility goes on at the subcellular level.
* When a cell divides, its chromosomal material splits, and movesapart to the two daughter cells.
* Organelles and vesicles in the cytoplasm move back and forth.
* Nutrients flow down the long thin fibers of neurons.
The prime movers for these three types of motion are molecularmotors called kinesins. These proteins travel along tracks in the cellcalled microtubules.
Myosin is a different type of protein motor; it drives musclecontraction, by interacting with filaments made from the protein actinto convert chemical energy into force.
Myosin and kinesin both harness chemical energy to generate motionthe way an engine burns gasoline to make a car move. That fuel isadenosine triphosphate (ATP), which the body produces bymetabolizing food.
Myosin's motor region is more than twice the size of kinesin's, andtheir amino acid sequences are dissimilar. Ditto their 2-D shape asseen by electron microscopy.
So cell biologists were in for a surprise when they compared theprotein's 3-D configuration by X-ray crystallography, whichmagnifies 10 times as much as the electron microscope. They sawthat structurally, myosin and kinesins are strikingly similar. Thissuggests that both motor proteins use a similar force-generatingstrategy _ nature imitating nature.
It's all spelled out in words plus crystallographic images in a recentissue of Nature, dated April 11, 1996.
_ Compiled By David N. Leff, Science Editor
(c) 1997 American Health Consultants. All rights reserved.