Thoracic
Khea Tan, MD (she/her/hers)
General Surgery Resident
Hackensack Meridian Jersey Shore University Medical Center, New Jersey, United States
Kelly Banas, PhD
Principal Investigator
Gene Editing Institute ChristianaCare, United States
Nicole Haas, MS
Staff Scientist
Gene Editing Institute ChristianaCare, United States
Natalia Rivera-Torres, PhD
Principal Investigator
Gene Editing Institute ChristianaCare, United States
Pawel Bialik, MS
Principal Investigator
Gene Editing Institute ChristianaCare, United States
Brittany Al-Atrache, MD
General Surgery Resident
Hackensack Meridian Jersey Shore University Medical Center, United States
Gregory Tiesi, MD, FACS, FSSO
Medical Director of Hepatobiliary Surgery
Hackensack Meridian Jersey Shore University Medical Center
Neptune, New Jersey, United States
Gregory Tiesi, MD, FACS, FSSO
Medical Director of Hepatobiliary Surgery
Hackensack Meridian Jersey Shore University Medical Center
Neptune, New Jersey, United States
Eric Kmiec, PhD
Executive Director and Chief Scientific Officer
Gene Editing Institute ChristianaCare, United States
Mice were intratumorally injected on days 0, 2 and 7 with R34G-Cas9 or a non-specific scrambled Cas9 versus control. All mice received intravenous low-dose chemotherapy (carboplatin plus paclitaxel) on days 3 and 10. Survival was tracked up to 50 days post initial intratumoral injection. All groups consisted of n = 12 mice. Group 1 received R34G-Cas9 with 12.5mg/kg carboplatin and 5mg/k paclitaxel. Median overall survival time was not reached as none of the mice died within the observation period (overall survival = 100%). Group 2 received scrambled-Cas9 with 12.5mg/kg carboplatin and 5mg/k paclitaxel. Median overall survival time was 33 days with an overall survival of 33% for the experiment. Group 3 received chemotherapy alone. Median OS time was also 33 days with an overall survival of 42%. Overall survival in Group 1 was statistically significantly longer compared to both groups (p < 0.5). (Figure 1)
Conclusions: CRISPR-Cas9 editing of NRF2, in an in vivo PDX mouse model, led to decreased chemoresistance and marked improvement in overall survival. To our knowledge, our tumor specific gene editing to restore drug activity is the first of its kind ever reported.