EXCLUSIVE:

FEATURES:

• Silence one gene at up to three sites

• Silence more than one gene

• No sense-strand based ‘Off-Target’ effects

• Available in pSUPER-MV, pSUPER-DV Forms

• Available as Synthetic complexes

• Easily designed at Oligoengine

SINGLE MOLECULE, MULTI-SITE RNA INTERFERENCE

[ MV-siRNA ]

SM

multivalent siRNA

Research Products Division of Halo-BioRNAi Therapeutics, Inc.

OFFICE1409 42nd Ave. E.Seattle, WA 98112

Phone: (206) 254-0200Fax: (206) 254.0300Toll-free: (800) 516.5446

Introduction

Multivalent siRNA [MV-siRNA} provides 3-in-1 siRNA capabilities for multi-site RNA interference. A single MV-siRNA can supress one gene at several sites,or suppress multiple genes all at once. This new design enables greater potencythan single siRNA, removes off-target elements, and replaces older ‘pooling’methods of traditional siRNA.

Triple siRNA potency, reduce off-target

TMmultivalent siRNAMult i -s i te RNA Inter ference

FOR RESEARCH PURPOSES ONLY. Other uses require a license from Halo-Bio RNAi Therapeutics, Inc.

TMmultivalent siRNAM u l t i - s i t e R N A I n t e r f e r e n c e

Secondary Strand

3’

Primary Strand

3’

5’

5’

Proximal B

ox

Distal Box

Dis

tal B

ox

Key Strand

Pro

ximal B

ox

5’

3’

Distal Box

Proximal B

ox

Figure I:HIV inhibitionby MV-siRNA

We have recently showed that a di-valent

MV-siRNA molecule against HIV’s GAG and

TAT genes was significantly more efficient

in inhibiting HIV replication than an siRNA

directed against Gag.

At 10 days post transfection, the inhibition

of HIV replication by the di-valent MV-siRNA

was about 3 times more important than

the one obtained with the siRNA molecule.

These results suggest that the slencing efficiency of each MV-siRNA strand is superior to the one of an siRNA molecule.Further studies will be performed to determine how a tri-valent MV-siRNA molecule compares to three independentsiRNAs in terms of silencing efficiency.

MV-siRNA is composed of three RISC-loadingRNA guide strands. Each RNA strand is pariallycomplimentary to the next, and form the threesiRNA-like arms of MV-siRNA complex. Eacharm of MV-siRNA contain a specific 3’ signalto initiate loading onto RISC.

: the molecule

MV-siRNA function similiarily to siRNA by guiding endonucleic activity viaRISC, but MV-siRNA triple the RISC mechanism. Each MV-siRNA arm is ableto load into RISC and guide the eventual catalysis of the target site. The threeguide strands of MV-siRNA can be designed against multiple sites on a singlegene or single sites on multiple genes- a novel function of MV-siRNA.

: the mechanism

5’

3’

Target Gene

5’

3’

3’

5’

5’3’

5’

3’

3’

5’

5’3’ RISC

Multiple Gene RNAi:Single site catalysis

Single Gene RNAi:Multiple site catalysis

5’

3’

Target Gene 1

5’

3’

Target Gene 2

5’

3’

Target Gene 3

5’

3’

3’

5’

5’3’

5’

3’

3’

5’

5’3’ RISC

MV-siRNA are available at:

WWW.OLIGOENGINE.COM