Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/143282
Title: RNA TRANS-SPLICING FOR SELECTIVE KILLING OF VIRUS-TRANSDUCED OR CANCER CELLS
Authors: SUSHMITA PODDAR
Keywords: splicing, trans-splicing, RNA, virus, cancer, suicide gene therapy
Issue Date: 22-Jan-2016
Citation: SUSHMITA PODDAR (2016-01-22). RNA TRANS-SPLICING FOR SELECTIVE KILLING OF VIRUS-TRANSDUCED OR CANCER CELLS. ScholarBank@NUS Repository.
Abstract: SPLICEOSOME-MEDIATED RNA TRANS-SPLICING REPRESENTS A POWERFUL TOOL FOR MICROSURGICAL REPAIR OR LABELLING OF ENDOGENOUS PRE-MRNA TRANSCRIPTS. WE INVESTIGATED HIGHLY EFFICIENT VIRAL RNA TRANS-SPLICING AND TRANSFERRED MOLECULAR FEATURES THEREOF TOWARDS THE DESIGN OF ARTIFICIAL TRANS-SPLICING RNA. USING COMPUTATIONAL RNA STRUCTURE DESIGN, WE IMPROVED BOTH ON-TARGET ACTIVITY AND SPECIFICITY OF TRANS-SPLICING RNA (TSRNA) IN A HERPES SIMPLEX VIRUS THYMIDINE KINASE/GANCICLOVIR SUICIDE GENE THERAPY APPROACH TARGETING THE A-FETOPROTEIN (AFP) OR HUMAN PAPILLOMA VIRUS-TYPE 16 (HPV-16) PRE-MRNAS. OPTIMIZED TSRNAS WERE DEMONSTRATED TO EFFICIENTLY TRIGGER DEATH OF HPV-16 OR AFP-POSITIVE CELLS. OUR OBSERVATIONS SUGGEST TRANS-SPLICING REPRESENTS A PROMISING APPROACH TO SUICIDE GENE THERAPY. FINALLY, WE DEMONSTRATED THAT TRANSCRIPTS WHICH ESCAPE NUCLEAR TRANS-SPLICING CAN SELECTIVELY BE ELIMINATED BY RNA INTERFERENCE (RNAI) IN THE CYTOPLASM, THUS SUPPORTING RNA SPLICING-BASED FUNCTIONAL GENE REPLACEMENT
URI: http://scholarbank.nus.edu.sg/handle/10635/143282
Appears in Collections:Ph.D Theses (Open)

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