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RAC Raises Issues With Nucleonics' HBV Trial


Late last year, the National Institutes of Health's Recombinant DNA Advisory Committee expressed a number of concerns about how Nucleonics has designed its proposed phase I trial for its expressed RNAi hepatitis B therapy, NucB 1000.

Chief among the issues raised by the RAC reviewers are the doses Nucleonics proposes to test in the clinical study, which the committee believes could potentially overwhelm patients' natural RNAi processes, and the company's decision to evaluate NucB 1000 only in mouse models in its preclinical research.

"The doses being put forward in [the trial's protocol] represent quite a large dose in relationship to previously conducted gene-therapy trials," Natasha Caplen, one of the RAC reviewers and head of the National Cancer Institute's Gene Silencing Section, said during the meeting. "One of our large concerns is that, when exploiting the RNAi mechanism, we don't interfere with its natural role in regulating endogenous gene expression."

In the trial's protocol, "we are now trying to extrapolate from mice — because all of the studies to date are in mice — the human situation," she added. "There may be a requirement for additional models."

The committee has no authority beyond making comments and recommendations.

During a relatively short question-and-answer session between the reviewers and members of Nucleonics' management, the company defended its proposed clinical trial, noting that its dosing schedule begins very low and that its protocols include numerous safety reviews.

Additionally, Nucleonics argued that there are few good animal models for hepatitis B since chimpanzees are no longer available due to animal protection rules.

Nucleonics President and CEO Bob Towarnicki said that his company would review and respond to the RAC's recommendations once they have been formally submitted, adding that Nucleonics' plan to file an investigational new drug application for NucB 1000 before the end of the year remains unchanged.

— Doug Macron

Short reads

It's official. Merck kicked off the new year by closing its $1.1 billion cash acquisition of Sirna Therapeutics. The acquisition plan was announced last October, and Sirna shareholders approved the deal in late December.

Antisense drug developer Genta has restructured itself following rejection of Geneasense, its lead chronic lymphocytic leukemia drug candidate, by the US FDA. As part of the restructuring, the company says that it has reduced its staff by about 35 percent.

Isis Pharmaceuticals announced that iCo Therapeutics has filed an investigational new drug application with US regulators to begin human testing of iCo-007, an antisense-based treatment for age-related macular degeneration and diabetic retinopathy.
Oxford BioMedica and Sigma-Aldrich have signed a joint license agreement giving access to their LentiVector gene-delivery technology to GlaxoSmithKline for research purposes.
Within the first half of this year, Dharmacon plans to publish a proposed set of standards for conducting RNAi screening experiments developed through its Genome-Wide RNAi Global Initiative consortium.

Mirus Bio signed a two-year deal with Pfizer to target and suppress the expression of certain genes. Mirus will study methods for optimizing gene silencing methods in animals.


US patent application 20060293272. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid. Inventors: James McSwiggen, Bharat Chowrira, Leonid Beigelman, Dennis Macejak, Shawn Zinnen, Pamela Pavco, et al. Assignee: Sirna Therapeutics. Filed: August 4, 2006.

This invention concerns methods and reagents for modulating gene expression in a number of applications, including use in therapeutic, diagnostic, target validation, and genomic discovery applications. It specifically relates to synthetic chemically modified small nucleic acid molecules capable of mediating RNAi against target nucleic acid sequences.

US patent application 20060282921. Transgenic plant-derived siRNAs for suppression of influenza virus propagation in mammalian cells. Inventors: Eric Lam, Man Lit Poon, Yuanxiang Zhou, Mee Len Chye, and Joseph Peiris. Filed: April 10, 2006.

According to the abstract, this invention covers plant-derived agents to interfere with the nonstructural NS1 gene from an influenza subtype. Specifically, the siRNAs exhibit strong inhibitory activity to NS1, which effectively suppresses replication of the influenza virus in mammalian cells.

Data point


In 2006, there were 518 research and review papers about microRNA research indexed by PubMed. This represents an increase of approximately 34 percent over the previous year.


The Scan

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Also Subvariants

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