Polyethylene glycol (PEG) conjugates for in vivo delivery of siRNA

CARB 54

Kathy Mills, kmills@alnylam.com, Ravi Braich, rbraich@alnylam.com, Klaus Charisse, kcharisse@alnylam.com, Tim Racie, tracie@alnylam.com, Iva Tourdjaarska, itourdjaarska@alnylam.com, Kallanthottathil G. Rajeev, rajeevk@alnylam.com, Tracy Zimmermann, tzimmermann@alnylam.com, and Muthiah Manoharan, mmanoharan@alnylam.com. Alnylam Pharmaceuticals, 300 Third St, Cambridge, MA 02142
In order to improve the pharmacokinetic properties of siRNAs, which are intrinsically poor binders to serum proteins and rapidly cleared through the renal system, we conjugated Apo-B siRNAs to polyethylene glycol (PEG) using a hydroxyprolinol linker. In contrast to the corresponding cholesterol conjugates, PEG-siRNA gene silencing was observed in the jejunum and not in the liver. Furthermore, the observed effect was dependent on the length of the PEG used. Synthesis of the conjugates, analytical characterization, and in vivo pharmacology will be presented.
 

General Posters
6:00 PM-8:00 PM, Tuesday, August 21, 2007 BCEC -- Exhibit Hall - B2, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Sci-Mix

Division of Carbohydrate Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007