Compugen Ltd. recently announced the development and validation of its Intracellular Drug Delivery (IDD) discovery platform for identification of cell-penetrating peptides. Compugen also announced that as part of the validation process for the new platform, more than 20 novel peptides, predicted and selected in silico, demonstrated the predicted cell-penetrating properties in initial experimental validation studies.

The delivery of biological molecules across selectively permeable cell membranes and into the cells represents a major challenge for the pharmaceutical industry. Furthermore, important classes of biological drugs now under development, such as therapeutic peptides and siRNA, need to enter the cell to be effective. Because most are unlikely to cross the surrounding protective membranes of cells on their own, they will require some type of delivery methodology. Cell-penetrating peptides offer the opportunity to provide the required intracellular targeting of therapy, either by delivery of a therapeutic molecule as “cargo,” or by the peptide itself.

Compugen’s newly developed IDD discovery platform enables the in silico identification of novel peptide sequences that are predicted to have the potential to penetrate the cell membrane. This new platform consists of various components from Compugen’s existing computational biology infrastructure and a series of proprietary machine-learning algorithms specifically designed for this platform. In a validation run of the platform, a number of peptides having various physico-chemical properties potentially relevant for different specific uses were predicted and experimentally evaluated. Their ability to penetrate into cells was assessed by two independent well-accepted in vitro assay systems. In these evaluations, more than 20 of these peptides were shown to possess cell-penetrating activity both by visual image analysis through confocal microscopy and quantitative measures performed by flow cytometry analysis.

The past 2 decades have seen an increasing research interest in cell membrane penetration and the discovery of various cell-penetrating peptides. In addition, the potential “cargo-carrying” capability of certain of these known cell-penetrating peptides has been demonstrated in the lab by various experimental techniques; however, this capability was only recently introduced to the clinic. Looking to the future, it is forecasted that the availability of a much wider portfolio of cell-penetrating peptides with improved properties will be required in order for this delivery methodology to meet the needs of the large number of biological molecules now being evaluated industry wide for therapeutic purposes. In this regard, Compugen intends to utilize its IDD platform to create a library of cell-penetrating peptides with properties specific to different cargos and/or tissues.

In addition to the substantial opportunity represented by “therapeutic cargo-carrying,” Compugen intends to integrate its IDD discovery platform with its other in silico therapeutic peptide discovery capabilities, such as the DAC Blockers platform, in order to create dual function peptides. These dual-function peptides will be designed to both penetrate the cell membrane and provide the required therapeutic intervention.