Science & Technology

THE DICERNA DIFFERENCE:
THE NATURAL SILENCING PATHWAY

RNA interference (“RNAi”) was first discovered in 1990 by Dr. Rich Jorgensen in petunias. Searching for a way to increase the intensity of the flowers’ color, Jorgensen and colleagues added copies of an enzyme known to be involved in pigmentation. But instead of enhancing the color, the additional copies caused the color to disappear. The flowers turned white. Later, in 1998, Drs. Andrew Fire and Craig Mello at the Carnegie Institution of Washington found that this phenomenon was caused by creation of double-stranded RNA, which triggered the reduced expression of the target gene. They won the 2006 Nobel Prize in Physiology or Medicine for their work. When RNA interference was first discovered in animals, the finding was made in fruit flies. This discovery led to the first wave of RNA interference-based therapeutics and target validation approaches. The mammalian RNAi pathway was only elucidated later and found to contain an additional component: the enzyme Dicer, a natural initiation point for the RNAi cascade. Dicer acts earlier in the pathway to prepare double-stranded RNA for processing. By introducing sequence-specific RNA templates on which Dicer can act, Dicerna has created a more potent and longer-lasting variant of RNA interference.

GREATER POTENCY FROM LONGER SEQUENCES

Using its Dicer Substrate Technology™, Dicerna can knock down the expression of a targeted gene in a way that is highly selective, specific and more potent than other RNAi approaches. The Dicer Substrate Technology is based on intellectual property that is both broadly enabling and distinct from other IP in the field.

GREATER POTENCY FROM LONGER SEQUENCES

GREATER DURATION OF EFFECT FROM
DICER SUBSTRATES

Dicerna’s 27mer RNAi therapeutics are based on Dicer Substrate Technology, which provides much longer-lasting knockdown compared to standard 21mers. Here the prolonged duration of effect in comparison to 21mers is shown.

GREATER POTENCY FROM LONGER SEQUENCES