Ribozyme/Antisense

moonshadow

Ribozyme/Antisense

Ribozymes (Rz) are catalytically active RNA molecules. Rz are able to cleave specific "target” messenger RNAs (mRNA), release the products, and attack the next mRNA. mRNAs are used as the "construction plans” for the biosynthesis of distinct proteins. If the construction plan is destroyed by cleavage, the protein in question can’t be made. Since their discovery, Rz have been the subject of extensive research efforts, with results which have been mostly disappointing.

The key to efficient Rz action is the identification of sites on the target mRNAs, which are accessible for cleavage. To this end, we have developed a proprietary library selection technique which allows us to determine optimal target sites. The innovative principle of our reagent is the use of specially designed, highly active Rz, which are synthesized in the target cell in a tissue-specific manner. That way they are active only in specific tissues of a patient. A second level of protection is afforded by our ability to target the liposomal delivery vehicle, in which the Rz are packaged, to specific cell types. Finally, the third level of safety is afforded by the inherent specificity of the Rz themselves. If the mRNA of the targeted infectious agent is not present, the Rz is not active against any other targets. These 3 levels of protection assure a significant level of biosafety for use of our therapeutic agents.

Based on our library selection of optimal target sites, we are also utilizing antisense oligonucleotides (ASO). ASO work by binding to specific "target” messenger RNAs, blocking their function. The bound mRNAs are targeted for destruction by cellular mechanisms, and cannot function as construction plans. Rz and ASO each offer selective advantages in particular applications, depending upon a number of factors.

ps:For in vivo studies, the Rz and ASO are being delivered to hepatocytes using liposomes targeted to liver with specific moieties. Extensive animal studies using ASO have documented a major inhibition of HBV replication in a transgenic mouse model, and Rz testing is now beginning. These studies are being funded under the auspices of a NIH program.