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Realizing the Promise of Therapeutic RNAi: Emerging Strategies for RNAi Delivery

Published by: Decision Resources

Published: Jan. 31, 2008 - 26 Pages


Table of Contents


Introduction

Mechanism of RNA Interference

Design of RNAi Research Reagents and Therapeutics

Delivery of RNAi Therapeutics

Alnylam’s Direct Delivery of Naked siRNA

Nastech Pharmaceutical’s Carrier-Mediated Technology

Systemic Delivery of siRNA Using SNALPs

Alnylam Pharmaceuticals

Sirna Therapeutics

Intellectual Property Issues

Alnylam Pharmaceuticals/MIT’s Lipidoid Nanoparticles

Alnylam’s Clinical Progress

Silence Therapeutics’ siRNA-Lipoplexes

RXi’s Interfering Nanoparticles

Intradigm’s TargeTran Nanoparticles

Covalent Conjugation of siRNA to a Targeting Molecule

Alnylam Pharmaceuticals

Duke University

Antibody-Mediated Targeting of siRNAs

Systemic Targeting of siRNAs to the Central Nervous System

Company Highlights

Alnylam Pharmaceuticals

Sirna Therapeutics

RXi Pharmaceuticals

Silence Therapeutics

Outlook for the Delivery of RNAi Therapeutics

Tables:

1. Select RNAi Therapeutics in Development

2. Select Technologies for Systemic Delivery of siRNAs

3. Select Companies Developing RNAi Therapeutics and/or Delivery Technologies

Figures:

1. Mechanism of RNA Interference

2. Structure of a Stable Nucleic Acid Lipid Particle (SNALP)

3. Schematic of Intradigm’s TargeTran Nanoparticles

4. Delivery of siRNAs to Neurons via the Acetylcholine Receptor

Abstract

The discovery of RNA interference (RNAi) has renewed interest in developing nucleic acid drugs based on targeting messenger RNAs (mRNAs). This field of research offers the potential to produce low-dose, nontoxic RNAi agents to treat important diseases. Venture capitalists have invested large sums of money in RNAi companies, and Big Pharma is acquiring and partnering with RNAi specialty companies. The success of RNAi therapeutics rests on the development of technologies that can deliver these agents to their targets.

Questions Answered in This Spectrum Report:
  • Several companies are focusing on RNAi-based therapeutics. Which are the leading companies in the field, and which ones are in partnership with or have been acquired by Big Pharma? What projects are they undertaking?
  • The holy grail for RNAi drug companies remains systemic delivery. Companies are competing furiously to develop viable systemic delivery methods. What are the promising technologies for systemic delivery, and which companies are at the forefront of delivery technology?
  • Opko Health’s bevasiranib is the most advanced RNAi therapeutic. It is in Phase III clinical trials for wet age-related macular degeneration. What other RNAi therapeutics have been developed and for what disease(s)? At what stage of development are they?
Scope:
  • SRNAi: Its mechanism of action.
  • Delivery of RNAi therapeutics: Direct delivery of naked siRNA, systemic delivery of siRNA using stable nucleic acid lipid particles (SNALPs), lipidoid nanoparticles, siRNA-lipoplexes, interfering nanoparticles, TargeTran nanoparticles, covalent conjugation of siRNA to a targeting molecule, antibody-mediated targeting of siRNAs, systemic targeting of siRNAs to the CNS.
  • Top companies in RNAi research: Alnylam Pharmaceuticals, Sirna Therapeutics, RXi Pharmaceuticals, Silence Therapeutics.


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