| Title: |
Evaluating a Targeted Cancer Therapy Approach Mediated by RNA |
| Authors: |
Woess, Katharina; Sun, Yuchen; Morio, Hanae; Stierschneider, Anna; Kaufmann, Anna; Hainzl, Stefan; Trattner, Lisa; Kocher, Thomas; Tockner, Birgit; Leb-Reichl, Victoria; Steiner, Markus; Brachtl, Gabriele; South, Andrew P.; Bauer, Johann W; Reichelt, Julia; Furihata, Tomomi; Wally, Verena; Koller, Ulrich; Piñón Hofbauer, Josefina; Guttmann-Gruber, Christina |
| Source: |
Department of Dermatology and Cutaneous Biology Faculty Papers |
| Publisher Information: |
Jefferson Digital Commons |
| Publication Year: |
2022 |
| Collection: |
Jefferson Digital Commons (Thomas Jefferson University, Philadelphia) |
| Subject Terms: |
Ct-SLCO1B3; cancer gene therapy; epidermolysis bullosa; ganciclovir; herpes simplex virus thymidine kinase; spliceosome mediated RNA trans-splicing; squamous cell carcinoma; Dermatology; Medicine and Health Sciences |
| Description: |
Conventional anti-cancer therapies based on chemo- and/or radiotherapy represent highly effective means to kill cancer cells but lack tumor specificity and, therefore, result in a wide range of iatrogenic effects. A promising approach to overcome this obstacle is spliceosome-mediated RNA trans-splicing (SMaRT), which can be leveraged to target tumor cells while leaving normal cells unharmed. Notably, a previously established RNA trans-splicing molecule (RTM44) showed efficacy and specificity in exchanging the coding sequence of a cancer target gene (Ct-SLCO1B3) with the suicide gene HSV1-thymidine kinase in a colorectal cancer model, thereby rendering tumor cells sensitive to the prodrug ganciclovir (GCV). In the present work, we expand the application of this approach, using the same RTM44 in aggressive skin cancer arising in the rare genetic skin disease recessive dystrophic epidermolysis bullosa (RDEB). Stable expression of RTM44, but not a splicing-deficient control (NC), in RDEB-SCC cells resulted in expression of the expected fusion product at the mRNA and protein level. Importantly, systemic GCV treatment of mice bearing RTM44-expressing cancer cells resulted in a significant reduction in tumor volume and weight compared with controls. Thus, our results demonstrate the applicability of RTM44-mediated targeting of the cancer gene Ct-SLCO1B3 in a different malignancy. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
English |
| Relation: |
https://jdc.jefferson.edu/dcbfp/158; https://jdc.jefferson.edu/context/dcbfp/article/1169/viewcontent/ijms_23_00575.pdf |
| Availability: |
https://jdc.jefferson.edu/dcbfp/158; https://jdc.jefferson.edu/context/dcbfp/article/1169/viewcontent/ijms_23_00575.pdf |
| Rights: |
http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.A94F1567 |
| Database: |
BASE |