RNAi compounds are made from a strand or strands of RNA that are manufactured by a nucleic acid (RNA) synthesizer. The synthesizer is programmed to assemble a strand of RNA of a particular sequence using the four kinds of nucleotide units (Adenine (“A”), Uracil (“U”), Cytidine (“C”) and Guanosine (“G”)) that match a small segment of the targeted gene. The hallmark of an RNAi compound is that it has a double-stranded region. The compounds can be of various lengths of nucleotide units (nt). As seen in the Figure below, the two strands can have overhangs (as shown on the far left), or they can have blunt ends (as shown in the middle and right). A single strand can form an RNAi compound by forming a structure (shown on the right) referred to as a hairpin.
Figure - Types of RNAi compounds The length and shape can affect the activity and hence the potency of the RNAi in cells. RXi prefers to use RNAi of the form without the overhangs as originally described by Dr. Craig Mello in the seminal patent application on RNAi. The RNAi compounds preferred by RXi can also optionally be of the hairpin shape. These RNAi compounds are distinct from the siRNA compounds used by many other companies developing RNAi therapeutics, and RXi calls this class of compounds rxRNATM. rxRNA is an alternative to classic siRNA used by many other companies developing RNAi therapeutics and is:
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up to x 100 more active than conventional siRNA (depending on the target site),
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nuclease resistant,
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readily manufactured,
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comprised of elements from RXi’s IP portfolio, and
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potentially more specific for the target gene.
