NEWS OF THE WEEK INORGANIC
CHEMISTRY
phy studies, the team reports that both ends of the chain are capped with iodine and that there are no bridging ligands supporting the five indium-indium single bonds. The research team includes Michael S. Hill and Ruti Pongtavornpinyo of Imperial College London and Peter B. Hitchcock at the University of Sussex. "We certainly weren't expecting C O M P O U N D COMPOSED group 14 elements, which readily the open-chain complex toformin of six indium atoms ar form molecular chains of various the way it did," says Hill, who led range in a linear chain has lengths, elements in group 13 (B, the study. He adds that, consider been synthesized by researchers in Al, Ga, In, and IT) are far less like ing earlier work that he and his England (Science ly to bond to one another in a lin colleagues conducted on indium 2006,3/7,1904). ear fashion, particularly in chains compounds and isoelectronic The study broad of three or more atoms. But now porystannanes, "I was hopingfora ens understand researchers have shown that under well-defined cyclic oligomer."Just ing ofmain-group therightcircumstances, indium the same, Hill points out that the surprising results are "completely metal chemistry can form linear oligomers. and may lead to By reacting indium iodide with reproducible." novel strategies a protonated N-xyfyl β-diketimi He hopes that the paper "will for preparing in nate and a strong potassium base, add another color to the palette of organic oligomers the scientists formed a hexaindium chemistry and prompt researchers and polymers. chain in which one β-diketiminate to examine the potential of inor Unlike car ligand is bound to each metal at ganic polymers more broadly."— bon and other om. On the basis of crystallogra MITCH JACOBY
A CHAIN OF SIX INDIUM ATOMS
SIX LITTLE INDIUMS Bonding bulky β-diketiminate ligands to indium directs the metal atoms to form a sixmembered linear chain. In is purple; I, red; C, black; and N, blue.
Group 13 element shows surprising ability to form a linear oligomer
A
ACS M E E T I N G
NEWS
RNAI ADVANCE liposome system delivers short RNAs that silence genes and reduce cholesterol SILENCE, PLEASE A liposomal system developed by Protiva Biotherapeutics was used for long-acting systemic delivery of siRNAs in monkeys.
12
T
C & E N / A P R I L 3, 2006
HE GENE-SILENCING TECH-
nique called RNA interference has moved a step closer to becoming a viable therapeutic approach. Scientists at Alnylam Pharmaceuticals in Cambridge, Mass., used RNAi in monkeys to silence the gene for apolipoprotein Β (ΑροΒ), a protein involved in cho lesterol metabolism. The study was published in the online edition of Na ture on March 26 (dx.doi. oig/10.1038/nature04688). MuthiahManohaian,vice presidentfordrug discov ery at Alnylam, described the work last week at the ACS national meeting in Atlanta.
Tracy S. Zimmermann and coworkers gave monkeys a single injection of a short interfering RNA (siRNA) in a liposomal for mulation optimizedfordelivery to the liver. Within 48 hours, expres sion of the ApoB gene in the liver dropped by more than 90%. The levels of ApoB, serum cholesterol, and low-density lipoproteins (com monly known as "bad" cholesterol) also dropped significantly. The ef fects lasted 11 days. In an earlier study with mice, the siRNA was conjugated to cho lesterol (C&EN, Nov. 15,2004, page 9). The liposomal delivery sys tem was effective with doses as low as 1 mg/kg of body weight. "We're continuing to optimize the use of chemical conjugates," says John
Maraganore, president and CEO of Alnylam. "At the same time, weVe been exploring other ways of delivering siRNAs systemicalry. We believe that multiple technolo gies can be brought to bear." John J. Rossi, a molecular bi ologist who studies RNAi at the Beckman Research Institute of the City ofHope in Duarte, Calif., cites as an important advance the fact that, to get a systemic effect, a lower dose is needed with the cur rent delivery system than with the cholesterol conjugate. Although Alnylam has yet to declare its first candidate for sys temic RNAi, the company contin ues to move toward clinical trials. "With liposomal technologies, we have a near-term opportunity and solution that can be used to begin to build our clinical pipe line," Maraganore says. "We're now in the position where we can begin to advance systemic RNAi therapeutics toward human clini cal testing as early as the next 18 to 2 4 months."—CELIA ARNAUD WWW.CEN-0NLINE.ORG
