NeuGene^® Antisense

What is antisense?

All human disease is linked to gene expression. The Human Genome Project (completed in 2003) paved the way for researchers to identify the genes most closely associated with human diseases.

Using modern methods of chemical synthesis, compounds can be made that bind to selected genetic material to block a disease process. One of the earliest approaches, pioneered by AVI BioPharma, is called antisense technology.

The term “antisense” arose because the synthetic compound is complementary to a gene’s messenger RNA (mRNA); that is, the “sense” strand that the body uses as a template to build specific proteins. When the antisense compounds bind to this sense strand, its protein building function is effectively shut off, like turning off a faucet.

Antisense compounds are made up of subunits linked together. Each subunit carries a genetic “letter” (A,T, G or C) that allows it to match with its pair on the messenger RNA) target. Although genetic letters are common to all antisense compounds, the chemical structures of the subunits and the linkages that hold them together vary widely. The linkages form what is referred to as the backbone.

These variations in the backbone’s chemistry differentiate AVI BioPharma’s NeuGene^® drug candidates from other, earlier–generation antisense technologies. NeuGene antisense technology is based on synthetic subunits, as opposed to modified natural materials. In addition, in NeuGene technology the linkages used to hold the subunits together are uncharged molecules. These key differences provide the pharmaceutical properties that are required for antisense technology to achieve broad clinical utility.

See How NeuGene Technology Works

Favorable Properties of NeuGenes

In preclinical and clinical studies, NeuGene antisense compounds have demonstrated advantageous pharmaceutical properties including stability, specificity, efficacy, delivery and safety.

AVI’s principal competitive advantage with its NeuGene antisense technology is the chemical structure of the compound backbone, which has been developed specifically to address the following pharmaceutical parameters:

Stability: Biological stability is principally determined by the resistance of the compound to degrading enzymes in the body. Because the NeuGene backbone has a unique synthetic structure, there are no human enzymes that will degrade it. As a result, NeuGene candidates have shown excellent stability in human clinical trials.

Efficacy and specificity: Efficacy refers to the efficiency with which antisense compounds block selected genetic targets. Specificity is how accurate the compounds are in blocking only the selected targets (and not other, unrelated targets). In direct comparison with other technologies, NeuGene compounds exhibit significantly better efficacy in inhibiting targeted genetic sequences and substantially greater specificity.

Delivery: To reach their genetic targets, antisense compounds must cross many barriers, including cellular and nuclear membranes. Research conducted in animal models and human clinical trials has shown that NeuGene antisense compounds are transported to targeted sites where they are functional.

Safety: Human clinical trial results indicate that NeuGene antisense agents have a promising safety profile. In the treatment of more than 400 patients, no serious safety–related adverse events have been observed.

Comparison of Gene-Targeted Technologies