this is a stock I got into. they are using nanoparticles to deliver RNA to stop protein processes in cancer cells (with no side effects at any dose rate) but the potential applications for this tech seem limitless. arwr has a number of subsidiaries that are doing well on their own.

there is a demonstration coming up in a few days IMO this is a short and long term play.

any DD / feedback would be appreciated, good trading everyone, HB

FROM THE LION.COM:

http://www.thelion.com/bin/forum.cgi?tf=wall_street_pit&msg=1920810&cmd=r

next leg, AARC presentation momo......

Nanoparticle mediated delivery of siRNA targeting RRM2 inhibits tumor growth of head and neck and lung cancers

Presentation Time: Tuesday, Apr 20, 2010, 9:00 AM -12:00 PM

Location: Exhibit Hall A-C, Poster Section 30

Poster Section: 30

Poster Board Number: 5

Author Block: Mohammad A. Rahman1, A.R.M. Ruhul Amin1, Xu Wang1, Dongsheng Wang1, Mark E. Davis2, Bingsen Zhou3, Yun Yen3, Zhuo Georgia Chen1, Dong M. Shin1. 1Emory Winship Cancer Institute, Atlanta, GA; 2Chemical Engineering, California Institute of Technology, Pasadena, CA; 3Department of Clinical and Molecular Pharmacology, City of Hope National Medical Center, Duarte, CA

Abstract Body: Inhibition of specific genes by small interfering RNAs (siRNA) offers a promising therapeutic approach in oncology. However, siRNA therapy is hindered by poor stability under physiological conditions and limited intracellular uptake. Ribonucleotide reductase subunit M2 (RRM2) is an essential protein for DNA synthesis and is responsible for the reduction of ribonucleotides to deoxyribonucleotides, providing a balanced supply of precursors for DNA synthesis and repair.

In this study we investigated the efficacy and mechanism of action of a targeted nanoparticle formulation of siRNA against RRM2. The clinical version of this nanoparticle is denoted as CALAA-01 and is currently used in a Phase I clinical trial. The nanoparticle consists of a cyclodextrin-containing polymer, a polyethylene glycol steric stabilization agent, and human transferrin as a targeting ligand for binding to transferrin receptors (TfR) that are typically up regulated in cancer cells. Initially, we screened several head and neck squamous cell carcinoma (HNSCC) and lung cancer cell lines and found various degrees of expression of TfR and RRM2. Suppression of RRM2 by transfection of 5 nM siRNA for 72 hours in vitro strongly inhibited the cell growth in HNSCC (Tu212~75% and M4e~60%) and in lung cancer cell lines (A549 and H460 ~80%).

Using xenograft (Tu212) as an in-vivo model, we found nanoparticles (10mg/Kg) injected via the tail vein in four dosing schedules (Day 1, 3, 8 and 10) significantly reduced RRM2 expression and its activity in xenograft tumors. RRM2 activity was reduced by an average 1.88-fold in the RRM2 siRNA treated group compare to the formulated control siRNA group (p=0.04). We monitored tumor growth in treated and control groups (8 mice in each group) for 28 days and found that tumor growth reduced by an average 2.9- fold in the treated group compared to formulated control siRNA (p=0.004). The nanoparticle delivered RRM2 siRNA significantly suppressed cell proliferation and induced apoptosis as evidenced by xenograft tumor tissue staining with Ki67 and terminal deoxynucleotidyl transferase dUTP nick and labeling, respectively. Mechanistic studies (in-vitro) have revealed siRNA-mediated suppression of RRM2 increases apoptosis in a p53-independent manner.

Interestingly, suppression of RRM2 by 5nM siRNA for 72 hours increased activation of caspase 9 and caspase 3 at least 2-fold with concomitant increase in the levels of cleaved poly-ADP-ribose polymerase (PARP), thus suggesting a vital role for p73 in the observed apoptosis through an intrinsic pathway. Thus this study demonstrates that targeted nanoparticles can deliver RRM2 siRNA to head and neck tumors in mice and highlights RRM2 as an excellent target to induce potent apoptosis and tumor growth inhibition. (Supported by NIH/NCI grant U54CA119338-04)