CSO: Dr. Nir Skalka
Circuit-Bio is a synthetic biology company developing an innovative unique platform of logical gene circuits for cancer immunotherapy.
The Company’s platform focuses on generating gene circuits able to locally and accurately produce a combination of multiple immune-stimulating proteins (immunomodulators) exclusively expressed in targeted tumor cells. Thus, the circuit selectively converts cancer cells into ‘Trojan horses’ utilize as an anti-tumor resource, that triggers a robust long-term anti-tumoral immune response. The immunomodulators’ output is tightly controlled by two de novo synthetic cancer-specific promoters (SPECS), and specificity enhance a Boolean logic AND gate, which enable multi-output gene expression only when both synthetic promoters are activated simultaneously. This emerging bio-convergence approach differentiates itself from other immunotherapy treatments by a unique tunable mode of action, and therefore can overcome some of the major obstacles arising from the treatment of immunotherapeutic drugs. The circuit modularity can be reflected by the ability to control and adapt each of the circuit components to the treated indication, such as selecting the most effective tumor-specific immunomodulators combination output.
Synthetic gene circuits is a branch in synthetic biology research field aimed to selectively engineer and insert genes into targeted living cells to perform desirable, tunable and controlled logical functions. This approach enables reprogramming living organism cells to perform a broad range of new functions, such as cellular responses to changing environmental conditions, protein production and even operate a “kill switch” mechanism (suicide gene). This approach can be a useful tool for clinical and therapeutic applications in cancer treatment, because, in cancer therapy, the capability of precisely targeting cancer cells is essential but yet can be very challenging.
Immunotherapy based treatments have revolutionized cancer treatment in recent years. Unfortunately, many cancer patients cannot benefit from these immunotherapies as their tumors are not detected by the immune system or acquire resistance to the treatment and relapse. In addition, immune-modulatory therapies are often toxic due to their recognition of target proteins and antigens on normal tissues. Our synthetic gene circuit approach aims to overcome the lack of highly specific tumor surface antigens, immunotherapy drug resistance, tumor-mediated immunosuppression and toxicity by introducing engineered synthetic gene-based logic gate circuits into the cancer cells, thus evoking a selective and effective immune response against them. Tumor-localized immunomodulators will minimize the adverse effects caused by off-target activity and enable the utilization of potent combinations that are too cytotoxic for systemic administration.
Circuit-Bio’s technology is relevant to many different types of cancer. Initially, Circuit-Bio will focus on two oncological indications with a high unmet need: breast cancer and colorectal cancer (CRC), the second and the third most common cancers, respectively. The use of traditional cancer treatments for breast cancer and CRC, often fail to cure metastatic and recurrent disease. The systemic treatment approach of most immune-oncology agents for breast cancer and CRC comes with considerable safety risks such as a pronounced autoimmune response. Therefore, despite the significant overall advances in immunotherapy, current immunotherapies are often ineffective for CRC and breast cancer.
Circuit-Bio’s synthetic gene circuit design will specifically select a variety of functional immunomodulator combinations optimized and specifically adapted to human CRC and breast cancer immunotherapy to overcome the immunotherapy challenges. Our overarching hypothesis is that using this approach can initiate a robust and self-propagating anti-tumor immune response in the patient’s immune system, with the ability to target cancer metastasis and maintain a sustained memory immune response even without further circuit support.
Nir Skalka, Ph.D. – CSO
Dr. Skalka holds a Ph.D. from the Faculty of Medicine at Tel Aviv University with a focus on CRC and the Wnt signal. He has extensive experience in molecular biology and biochemistry methods, cancer research, immunology and in vitro and in vivo mouse cancer models. Before establishing Circuit-Bio, Dr. Skalka held various positions such as R&D scientist at Diabest Botanical Drugs, a drug development company for type 2 diabetes, and head of the immune-oncology team at Aummune (A spin-off from Augmanity Nano), a personalized medicine drug discovers company for cancer immunotherapy.
Lior Nissim, Ph.D. – Inventor
Dr. Nissim leads the applicative synthetic biology lab at the Hebrew University of Jerusalem Hadassah Medical School. He is an expert in the field of synthetic biology that combines biology, medicine and engineering principles, developing synthetic biology platforms for basic research and biomedical applications. During his Ph.D. at the Weizmann Institute of Science, he developed the very first synthetic gene circuit that actuated Boolean logic to precisely target cancer cells. Dr. Nissim performed his postdoctoral training at the Massachusetts Institute of Technology (MIT) synthetic biology center.