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Strands: Feb 26, 2009

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Tekmira Data Shows Improvements in SNALP Therapeutic Index, Publishes Data on Cancer Drug Candidate

Tekmira Pharmaceuticals this week announced the presentation of data showing that the therapeutic index of its stable nucleic acid lipid particles could be improved five to ten times over existing versions of the siRNA delivery technology through the incorporation of novel lipids.

The company said the data were unveiled at Asia TIDES Oligonucleotide and Peptide Technology and Product Development Conference in Tokyo.

"These improvements were made with SNALP formulations designed for delivery of siRNA to targets both in and outside of the liver," Tekmira said. "Furthermore, the formulation improvements were achieved without inducing adaptive immune responses."

Separately this week, Tekmira researchers published data in the Journal of Clinical Investigation showing that SNALP-based delivery of siRNAs targeting polo-like kinase 1 can effectively kill cancer cells and decrease tumor burden in mouse models.

Tekmira is developing an siRNA-based drug against PLK1 as a treatment for solid tumors. The company expects to begin clinical testing of the treatment in the second half of this year (see RNAi News, 11/20/2008).


MDRNA Data Shows UsiRNAs Capable of Target Gene Silencing In Vivo

MDRNA said this week that it has presented data showing that its so-called UsiRNAs were capable of triggering significant inhibition of a target gene, apolipoprotein B, in a rodent model.

The data were presented at Asia TIDES Oligonucleotide and Peptide Technology and Product Development Conference in Tokyo, MDRNA said.

UsiRNAs are duplex siRNAs that are modified with non-nucleotide acyclic monomers, called unlocked nucleobase analogs, in which the bond between two adjacent carbon atoms of ribose is removed, according to the company.

"Placement of UNA within UsiRNA minimizes the potential for off-target effects by the guide strand, as well as undesired activity of the passenger strand," MDRNA said. "Further, the change in sugar structure renders this unlocked nucleobase analog conformationally flexible," which allows the oligo to avoid cytokine induction and provides protection from nuclease degradation.

The Scan

Germline-Targeting HIV Vaccine Shows Promise in Phase I Trial

A National Institutes of Health-led team reports in Science that a broadly neutralizing antibody HIV vaccine induced bnAb precursors in 97 percent of those given the vaccine.

Study Uncovers Genetic Mutation in Childhood Glaucoma

A study in the Journal of Clinical Investigation ties a heterozygous missense variant in thrombospondin 1 to childhood glaucoma.

Gene Co-Expression Database for Humans, Model Organisms Gets Update

GeneFriends has been updated to include gene and transcript co-expression networks based on RNA-seq data from 46,475 human and 34,322 mouse samples, a new paper in Nucleic Acids Research says.

New Study Investigates Genomics of Fanconi Anemia Repair Pathway in Cancer

A Rockefeller University team reports in Nature that FA repair deficiency leads to structural variants that can contribute to genomic instability.