Technology- 1. Selective Gene Therapy

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The gene therapy activator is given to the patient . An “intelligent light source” is used to induce therapy in specific target cells.

The current treatment paradigm for patients with cancer involves the combination of surgery, radiation and chemotherapy. This approach of a multimodality treatment has specific types of limitation. 

1). The chemotherapy is broadly distributed to the patient’s body resulting in toxicity to normal cells. The chemotherapy therapeutic index is the difference in the ability of the therapy to kill a patient’s tumor versus the ability of the therapy to kill the patient’s normal cells. 

2). In addition, a specific subset of cells exists within a patient’s tumor known as cancer stem cells [1]. These particular cells are thought to give rise to subsequent recurrence, therapy resistance and metastases that kill a patient. These subset of cells divide very slowly and may take up to a month to divide [1]. 

3).  Because chemotherapy can be tolerated only for a short period of time, a subset of cells that are not dividing evade the chemotherapy treatment.

The inducer of the therapy is a plant steroid which has been purified  [3]. This steroid is without side effects because humans do not have the receptor for this steroid [4]. In addition, we have created sustained release pellets of this plant steroid which to date have been demonstrated to induce gene expression for a period of up to three months [5, 6]. This allows us to sustain the treatment for the patients and thereby avoid the prior problems of tumor recurrence based on a subset of non-dividing cells in the patient’s tumor. 

The gene therapy delivery can be delivered at a single cell level making it by far the most precise gene therapy delivery system known.

1. Velasco-Velazquez, M., Yu, Z., Jiao, X., Pestell, R.G., Cancer stem cells and the cell cycle: targeting the drive behind breast cancer. Expert Rev. Anticancer Ther. 2009 Mar., 9(3), 275-279.

2. Lin, W., Albanese, C., Pestell, R.G., Lawrence, D.S., Spatially discrete, light-driven protein expression. Chem Biol. 2002 Dec; 9(12):1347-53.

3. Albanese C, Reutens AT, Bouzahzah B, Fu M, D'Amico M, Link T, Nicholson R, Depinho RA, Pestell RG., Sustained mammary gland-directed, ponasterone A-inducible expression in transgenic mice. FASEB J. 2000 May;14(7):877-84.

4. Albanese C, Hulit J, Sakamaki T, Pestell RG., Recent advances in inducible expression in transgenic mice. Semin Cell Dev Biol. 2002 Apr;13(2):129-41. Review

5. Sakamaki T, Casimiro MC, Ju X, Quong AA, Katiyar S, Liu M, Jiao X, Li A, Zhang X, Lu Y, Wang C, Byers S, Nicholson R, Link T, Shemluck M, Yang J, Fricke ST, Novikoff PM, Papanikolaou A, Arnold A, Albanese C, Pestell R. Cyclin D1 determines mitochondrial function in vivo. Mol Cell Biol. 2006 Jul;26(14):5449-69.

6. Wang C, Pattabiraman N, Zhou JN, Fu M, Sakamaki T, Albanese C, Li Z, Wu K, Hulit J, Neumeister P, Novikoff PM, Brownlee M, Scherer PE, Jones JG, Whitney KD, Donehower LA, Harris EL, Rohan T, Johns DC, Pestell RG., Cyclin D1 repression of peroxisome proliferator-activated receptor gamma expression and transactivation.
Mol Cell Biol. 2003 Sep;23(17):6159-73.