You must read this just-published progress report on siRNA-based therapeutics written by ALNY scientists (Judy Lieberman is a prof. at Harvard Med, but she is with the ALNY board). If you register it is free. siRNA is moving into clinics with lightening speed ...
Summary RNAi has advanced from research discovery to clinical trials with lightning speed � from the Nobel-prize winning discovery in 1998 showing that long dsRNA could silence gene expression in Caenorhabditis elegans1, to the publication in 2001 showing that short synthetic siRNA could induce RNAi in mammalian cells2, to the present day when three different RNAi therapeutics are in human clinical trials. The RNAi revolution has fundamentally changed our understanding about how gene expression is regulated and has provided powerful new tools for biological research and drug discovery. It has opened the way for a new type of therapeutic with the potential to treat a wide array of diseases.
The principal challenge that remains in achieving the broadest application of RNAi therapeutics is the hurdle of delivery. The main barriers to successful RNAi delivery in vivo involve achieving proper pharmacokinetics to ensure drug exposure to the relevant target cell type and harnessing mechanisms to promote cellular uptake and the release of the drug into the cytoplasm. Progress has been made on this front through the use of covalent conjugation, non-covalent complexes and nanoparticles, but targeted delivery has yet to be optimized for most cell types and tissues. Solutions will probably need to be tailored for each target cell type and disease indication. In identifying and optimizing delivery solutions, the use of reporter systems (either endogenous cell-type specific genes or transgenes) could greatly expedite the process. Likewise, in optimizing formulations, it is vital that the key parameters of efficacy and safety are assessed in parallel to rapidly arrive at the formulations which have the greatest therapeutic window.
As the challenge of siRNA delivery is met, it will be possible to advance RNAi therapeutics rapidly into clinical studies for many diseases, including some which remain untreatable or poorly treated by conventional drugs. Ongoing clinical trials of siRNA drugs for AMD and RSV infection will be the first testing ground for whether RNAi therapeutics can live up to their potential as a revolutionary new class of drugs.