NEWS OF THE WEEK BIOMATERIALS
DNA NANOTUBES Made almost entirely of DNA, tubes might be useful for gene therapy
T
HE FIRST LAYERED NANO-
tubes composed almost entirely of DNA have been created. Layers of DNA in the nanotubes are held together by hybridization of a series of DNA strands. The nanotubes fall apart when heated, releasing singlestranded DNA. The nanotubes were synthesized and characterized by chemistry professor Charles R. Martin and coworkers Shifeng Hou and Jiahai Wang at the University of Florida, Gainesville (J.Am. Chem. Soc, published online May 25, dx.doi.org/10.1021/ja042343t). "These nanotubes might prove to be the ultimate DNA delivery vehicles—for treatment of genetic-based disorders, for example—because the nanotubes are essentially all DNA," Martin says. The DNA nanotubes are constructed in the 100-nm-diameter pores of alumina membranes. A diorganophosphonate "skin" is deposited in the pores, and Zr(IV) is used to link the diorganophosphonates to phosphonate groups on the end of a single-stranded DNAstrandThe strand's sequence is partially complementary to that of a second single-stranded DNA, and thus the two strands can hybridize. Similarly, the second DNAstrand hybridizes with a third DNA strand. The resulting cylindrical assemblies—three layers ofDNA plus the linkers and skin—are then released by dissolution of the template, yielding nanotubes made almost entirely of DNA. The paper focuses primarily on nanotubes madefrom15-base DNA strands, but Martin and coworkers also can prepare nanotubes from 8- and 12-base DNAs. "The DNA molecules WWW.CEN-0NLINE.ORG
composing these tubes can be varied at will," they note. "I have not seen similar approaches based on template construction of DNA nanotubes in which the DNA can eventually be liberated from the support," comments associate researcher Alberto Bianco of the Institute of Molecular & Cellular Biology at the French National Center for Scientific Research in Strasbourg. In previous work, researchers have made DNA-containingnanotubes by depositing DNA on a substrate and then functionalizing the DNAin various ways. But in the new nanotubes, the DNA content is more predominant, and Martin's approach "allows better control of the DNA nanotube structure," says Bianco, whose research interests include carbon nanotube biofunctionalization. The new nanotubes "could act as vehicles to deliver the DNA of which they are composed,"
IMPOTENCE
— Outer skin former • Zr(IV) linker
Bianco says. "In general, DNA DNA TUBE Crossdoes not cross cell membranes sectional view of DNA easily, and as a result, rates of nanotube with transfection [incorporation of exploded view of DNA into genes} are very low. nanotube wall. Methods to improve transfection are based on the formation of complexes between DNAand suitable carriers, such as liposomes, dendrimers, cationic polymers, and, more recently, carbon nanotubes." The new DNA nanotubes could make it possible to transfer DNA without separate carriers, but this would necessitate "that these tubes are able to cross the cell membrane and reach the nucleus," which has yet to be demonstrated, Bianco notes.— STU BORMAN
DRUGS
Blindness Concerns Hit A Stagnating Market
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ews late last month that federal authorities are investigating the use of Pfizer's Viagra and other impotence drugs for a possible link to a handful of cases of blindness in men only adds woes to a market that may be stagnating. FDA is acting on 43 reports of blindness caused by non-arteritic anterior ischemic optic neuropathy (NAION) among patients taking drugs for erectile dysfunction. Of these, 38 had taken Viagra; four had taken Cialis, from Eli Lilly and Icos; and one had taken Bayer's Levitra. The number of men taking impotence drugs is estimated at more than 25 million, with about 23 million taking Viagra. The potential world market is estimated at 189 million patients. The market for these drugs began to sput-
ter in 2004, six years after FDA approved Viagra. Manufacturers reported $2.4 billion in sales, at least $1 billion below analysts' earlier forecasts. Pfizer attributed Viagra's 11% drop in sales last year largely to competition from newcomers Cialis and Levitra. Analysts cite limited health care coverage for erectile dysfunction drugs and patients' embarrassment about discussing impotence problems with physicians as the primary factors limiting growth. Pfizer issued a statement last week claiming there is no evidence showing that NAION occurred more frequently in men taking Viagra than in men of similar age and health who did not take the drug. Pfizer cited 103 clinical trials with 13,000 patients in which no case of NAION was reported.-RICK MULLIN
C & E N / J U N E 6. 2005
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