| Added by | lklinares |
|---|---|
| Group name | EquipeLL |
| Item Type | Journal Article |
| Title | TAG-RNAi overcomes off-target effects in cancer models |
| Creator | Champagne et al. |
| Author | Julien Champagne |
| Author | Laetitia K. Linares |
| Author | Benjamin Maurel |
| Author | Alexandre Zampieri |
| Author | Maeva Moreno |
| Author | Ivanna Fuentes |
| Author | Emeric Dubois |
| Author | Dany Severac |
| Author | Adrien Decorsière |
| Author | Frédéric Bienvenu |
| Abstract | RNA interference offers therapeutic opportunities for the clinical targeting of otherwise undruggable oncogenes. However RNAi can have off-target effects that considerably increase treatment risks. To manage these side effects and allow an easy subtraction of their activity in healthy tissues, we present here the TAG-RNAi approach where cells that are not designated targets do not have the mRNA tag. Using TAG-RNAi we first established the off-target signatures of three different siRNAs specific to the Cyclin D1 oncogene by RNA-sequencing of cultured cancer cells expressing a FLAG-HA-tagged-Cyclin D1. Then, by symmetrical allografts of tagged-cancer cells and untagged controls on the left and right flanks of model mice, we demonstrate that TAG-RNAi is a reliable approach to study the functional impact of any oncogene without off-target bias. Finally we show, as examples, that mutation-specific TAG-RNAi can be applied to downregulate two oncogenic mutants, KRAS-G12V or BRAF-V600E, while sparing the expression of the wild-type proteins. TAG-RNAi will thus avoid the traditional off-target limitations of RNAi in future experimental approaches. |
| Publication | Oncogene |
| Volume | 39 |
| Issue | 4 |
| Pages | 935-945 |
| Date | 01 2020 |
| Journal Abbr | Oncogene |
| Language | eng |
| DOI | 10.1038/s41388-019-1020-2 |
| ISSN | 1476-5594 |
| Library Catalog | PubMed |
| Extra | PMID: 31558799 |
| Tags | Animals, Cell Line, Tumor, Cyclin D1, Humans, Mice, Mice, Nude, Mutation, Neoplasms, original, Proto-Oncogene Proteins B-raf, Proto-Oncogene Proteins p21(ras), RNA Interference, RNA, Small Interfering |
| Date Added | 2024/12/03 - 09:12:56 |
| Date Modified | 2024/12/03 - 09:12:56 |
| Notes and Attachments | PubMed entry (Attachment) |
Institut de Recherche en Cancérologie de
