Our Technology

Elimination of pro-inflammatory senescent cells has been shown to suppress cancer and rejuvenate tissues by restoring stem cell niches to their healthy state.

Two distinct senolytic approaches will be pursued independently or in combination, to eliminate senescent epithelial cells, associated with pre-cancerous, aging-related lesions:

  • Expression of a rapamycin-sensitive allele of the pro-apoptotic protein, Caspase-9 will be restricted to senescent cells using a p16INK4 promoter.
  • Expression of a senolytic peptide, derived from FOXO4 shown to disrupt interactions of p53 with FOXO4 in senescence cells (BaarMP17) will be overexpressed from a p16 or constitutive promoter.

¡Transgenes will be encoded by miniaturized plasmids, such as “minicircles” (MCs), and these will be delivered along with permeability enhancers to epithelial cells within a peptide- or polymer-based nanoparticle by topical ointment or biodegradable microneedle patch. Once adjacent to cells, NPs are endocytosed and are designed to rapidly escape from endosomes prior to biodegradation and release of transgene-encoding DNA within the cytosol.

We plan to investigate both transient expression of senolytic proteins and long-term chromatin integration regulated by the senescence-dependent p16 promoter, or an enhanced derivative. [We are also working on a membrane-permeable derivative of the sp that should spread to non-transfected cells.]