FANA is a technology platform composed of antisense oligonucleotide (AON) chemistries. An AON suitable for use as a therapeutic must bind tightly to its complementary target, elicit degradation of the target by the cellular enzyme RNase H, demonstrate efficacy in relevant in vitro and in vivo models of disease, and have suitable pharmacokinetic properties and physiochemical characteristics of a drug-like molecule (solubility, low non-specific binding to serum and cellular proteins, stable to degradation, etc).
In addition, Topigen claim that the AON manufacturing process is cost effective. Topigen' AONs have a proprietary chemical backbone composed of arabinose (ANA) or 2'-fluoroarabinose. Native RNA has a backbone of ribose, a stereoisomer of arabinose.
Simply speaking, the sugar chain that links ANA/FANA antisense molecules has a 2'-substitution in the "up" orientation, as opposed to the "down" orientation for ribose. This alteration in nucleotide sugar stereochemistry imparts several improvements to Topigen's AONs compared to other oligonucleotide chemistries.
"This new chemistry platform significantly improves the functionality of oligonucleotides for gene targeting and silencing and offers an alternative to the traditional antisense and RNAi approaches," said Dr Masad Damha, inventor of FANA and a professor of chemistry at McGill University.
In a series of studies comparing available gene modulating chemistries, FANA showed improvement in target affinity and duration of gene response while improving efficacy and safety. FANA significantly enhances nuclease resistance, providing lower dosage requirements and the potential for improved systemic administration.
"This new chemistry has the potential to effectively address some previously identified shortcomings of older antisense-based drugs," said Alan Gewirtz, professor of medicine at University of Pennsylvania, division of Hematology/Oncology.
"The ability to achieve a specific, long-lasting knockdown of a targeted gene will represent a true advance in the field and hopefully stimulate renewed interest in the area of therapeutic oligonucleotides," he added.
The characteristics of FANA could be advantageous for a wide variety of therapeutic gene modifying applications, including topical and systemic administration - areas of great importance in the drug discovery industry.
Topigen is currently developing a novel, multi-targeted drug product for COPD utilising FANA technology. Delivered via aerosol, the product (PD-3) is designed to inhibit gene expression pathways linked to the progressive airway remodeling associated with the disease. The drug candidate is scheduled to enter clinical trials in 2007.