Traversa's siRNA delivery technology is specifically designed to avoid the physical size and bioavailability problems inherent in the Liposome/cationic-lipid approach. The technology is non-cytotoxic, delivers to the entire cell population and all cell-types tested, and is dramatically smaller than a liposome. The Company expects the technology to provide improved pharmacokinetics, distribution and bioavailability over other methods. The technology supports delivery to primary and tumor cells, T cells, B cells, Macrophage, neuronal cells and human stem cells, where other approaches have failed. This ability to induce RNA interference in entire cell populations and all cell types in a non-cytotoxic fashion is unique to Traversa's technology and provides the Company's competitive advantage.

Traversa's siRNA delivery technology (PTD-DRBD) is a protein comprised of multiple Peptide Transduction Domains (PTD) linked to a Double-stranded RNA Binding Domain (DRBD). The PTD portion of the protein induces delivery into the cell through a fluid-uptake mechanism that all cells perform, called macropinocytosis. The DRBD portion of the protein initially binds to the siRNA, and later releases the siRNA once inside the cell.

Figure 1 provides two crystal structure views of a siRNA molecule coated and protected by four Traversa PTD-DRBD molecules.

PTD-DRBD mediated uptake of siRNA therapeutics occurs by initial binding to cell surface proteoglycans, stimulating macropinocytosis (Figure 2).  The PTD-DRBD carries the siRNA into the cell within a macropinosome.  As the macropinosome enters the cell, the pH drops inside the vesicle, the siRNA dissociates from the PTD-DRBD and the siRNA escapes into the cytoplasm.  The siRNA then loads into the RNA Induced Silencing Complex (RISC) to induce a selective RNAi response.

Table 1 illustrates the percentage of cells that experience siRNA delivery and RNAi response with Traversa's PTD-DRBD vs. Liposome and Lipofection delivery approaches.