NEWS OF THE WEEK
PROMISING POM-POMS THERAPEUTICS: Nucleic acid structures enter cells readily, control gene expression
Spherical PNANs (blue pom-poms) traverse cell membrane (brown and blue sandwich structure) by interacting with endocytosisinducing receptor (light and dark green).
reports a new form of synthetic DNA and RNA that looks like cheerleader pom-poms and can enter cells readily and regulate genes (J. Am. Chem. Soc., DOI: 10.1021/ja203375n). These polyvalent nucleic acid nanostructures (PNANs) could prove to have therapeutic effects by controlling the expression of diseaserelated genes, their creators say. Nanoscience expert Chad A. Mirkin and coworkers at Northwestern University developed PNANs and are collaboratively pursuing their use to treat a wide variety of diseases with genetic bases, including glioblastoma, a form of brain tumor for which new therapies are needed. They also are investigating the use of PNANs to speed wound healing and treat psoriasis, neurological diseases, and cardiovascular conditions, Mirkin says. PNANs are composed of DNA and/or RNA strands that radiate from a central point, where they are synthetically cross-linked. Synthetic DNA and RNA oligomers and PNANs can inhibit cellular gene expression by blocking mRNA-to-protein translation. But synthetic DNA and RNA strands typically do not enter cells readily, Mirkin says. That’s because single strands
COURTESY OF CHAD MIRKIN
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RESEARCH TEAM at Northwestern University
don’t interact efficiently with cell-surface receptors that control endocytosis, the process by which cells engulf extracellular molecules, he explains. PNANs enter cells more easily because their high nucleic acid surface densities, oriented strands, and large particle sizes allow them to interact efficiently with the endocytosisinducing gatekeepers on cell surfaces. Transfection agents such as polymers, liposomes, peptides, or viruses can enhance entry of synthetic DNAs and RNAs into cells. But these carriers can be toxic, immunogenic, and resistant to breakdown and may therefore cause side effects. By obviating the need for transfection agents, PNANs take concerns about transfection agent toxicity and side effects “completely out of the equation,” comments Dan Feldheim of the University of Colorado, Boulder, a specialist in medicinal nanostructures. Another important advantage of PNANs is that they resist enzymatic breakdown by nucleases. This enables them to last longer in the body—and more effectively knock down genes—than most synthetic DNA and RNA strands. In their paper, Mirkin and coworkers demonstrate that RNA-based PNANs can enter squamous cancer cells and inhibit the expression of epidermal growth factor receptor via an RNA interference mechanism. PNANs are actually core-free versions of constructs Mirkin’s group developed earlier—DNA and RNA oligomers attached to gold-nanoparticle cores, which also enter cells readily. “I was excited to see that the gold core could be removed so easily without compromising the function of the oligonucleotide shell,” Feldheim says. Nanomedicine specialist Joseph M. DeSimone of the University of North Carolina, Chapel Hill, says PNANs could “change the way people think” about nucleic acid therapeutics. They could “open up a lot of new approaches,” he says. “People are clearly going to try to build on this and see what other nucleic acid complexes one can make that will undergo similar cell internalization.”—STU BORMAN
ACADEMICS U.S. team selected for chemistry olympiad in Turkey Capping a nationwide competition, a team of four high school students will represent the U.S. at the 43rd International Chemistry Olympiad (IChO) in Ankara, Turkey, on July 9–18. The team will compete for medals alongside students from more than 70 other countries. The team members are Konstantin Borisov, North Allegheny Senior High School, Wexford, Pa.; Tayyab Shah, Vestal High School, Vestal, N.Y.; Elmer Tan, John P. Stevens High School, Edison, N.J.; and Joe Tung, Gretchen A. Whitney
High School, Cerritos, Calif. If any team member is unable to go, Kevin Yan of Thomas S. Wootton High School, Rockville, Md., and Sriram Pendyala of Mira Loma High School, Sacramento, Calif., are the alternates. The team was assembled on June 14 at the conclusion of an intensive two-week U.S. National Chemistry Olympiad study camp organized by the American Chemical Society and held at the U.S. Air Force Academy in Colorado Springs. The 20 students who participated in the camp
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were selected from a pool of approximately 10,000 students from around the country. Team mentor Kris Fletcher, a senior chemist at Chromatic Technologies, says the four students chosen for the U.S. team “not only demonstrated extraordinary understanding of the material tested as well as exemplary lab skills, but they also showed a level of maturity, respect, and responsibility we think are required to be good ambassadors of the U.S. at IChO.”—LINDA WANG
