rxRNA™: Next Generation RNAi Compounds
RNA was not designed by nature to be a therapeutic; therefore scientists have taken steps to make the RNA compounds behave in a drug-like manner. Most RNAi compounds are duplexes of two strands of chemically synthesized RNA and vary significantly in efficacy, stability and specificity. The compounds can have various chemical modifications and can be of various lengths (i.e. with different number of nucleotide units). The structural diversity of these compounds, which forms the basis for developing effective RNAi therapeutics, is derived by a combination of the length of the sequence, the specific nucleotide sequence (genetic code), and the configuration of chemical modifications associated with the sequence.
RXi uses its own version of RNAi compounds – rxRNA™ – developed by our team of world-class scientists. These novel compounds include rxRNAori™, rxRNAsolo™, and sd-rxRNA™ (or "self-delivering" RNA) and provide an advanced alternative to conventional siRNAs, defining the next generation of RNAi technology. rxRNA compounds are designed specifically for therapeutic use and contain many of the properties that are needed to advance RNAi based drugs into the clinic. rxRNA compounds are:
- up to 100x more active than conventional siRNA (depending on the target site)
- more resistant to nuclease degradation
- readily manufactured
- potentially more specific for the target gene
- more reliable at blocking immune side effects than conventional siRNA, and
- in the case of sd-rxRNA, have the unique ability to be 'self delivering', without the need for any additional delivery vehicle.
rxRNAori
This configuration has some similarities to classic siRNA in that it is composed of two, short, equal length RNA strands. We have found that by using a somewhat longer length (25 bp), removing the overhangs and using proprietary chemical modification patterns we achieve a higher hit rate of very potent (picomolar potency) compounds in a given target sequence. These rxRNAori compounds are modified to increase resistance to nucleases and to prevent off-target effects including induction of an immune response. These novel RNAi compounds are distinct from the siRNA compounds used by many other companies developing RNAi therapeutics in that they are designed specifically for therapeutic use and offer many of the properties that we believe are important to the clinical development of RNAi-based drugs.
For more information on rxRNAori, please refer to RXi’s Poster, January 2010, Keystone Symposia on RNA Silencing: Mechanism, Biology and Application.
rxRNAsolo
This novel configuration has been termed rxRNAsolo because it is composed of a single RNA oligonucleotide strand (27 nt long), with silencing potency equal to conventional RNAi triggers. This configuration also makes use of carefully placed and selected chemical modifications to introduce properties for therapeutic use, as described above. This new class of RNAi compounds has the potential to further reduce off-target effects and manufacturing costs and may thus offer additional advantages for use in research and therapeutic applications.
For more information on rxRNAsolo, please refer to RXi’s Poster, January 2010, Keystone Symposia on RNA Silencing: Mechanism, Biology and Application.
sd-rxRNA
"Self-delivering" rxRNA (sd-rxRNA) compounds are novel RNAi compounds that are modified to enable delivery to target cells and organs and efficient cellular uptake without the use of any delivery vehicle. A combination of at least three design characteristics is required for activity:
- Specific, proprietary chemical modifications
- A precise number of chemical modifications and
- Reduction in oligonucleotide content
For more information on sd-rxRNA compounds, please refer to RXi’s Posters, January 2010, Keystone Symposia on RNA Silencing: Mechanism, Biology and Application:
