Targeting Cancer Cells Using LNA-Modified Aptamer-siRNA Chimeras

Nucleic Acid Therapeutics
Nithya SubramanianSubramanian Krishnakumar

Abstract

Aptamers are chimerized with drug or antisense oligos or nanoparticles to generate targeted therapeutics for cancer. Aptamer chimerized siRNA rescues nonspecific delivery and, thereby, enhances the availability of siRNA to target cells. EpCAM RNA aptamer (EpApt or Ep) has potential for siRNA chimerization due to its secondary structure. Stathmin and survivin proteins are reported to aid oncogenicity in retinoblastoma (RB), breast cancer and other cancers. Thus, chimerization of EpCAM Apt with siRNA against survivin and stathmin, respectively, was performed by incorporating Locked Nucleic Acid (LNA) modification. The LNA-modified chimeric aptamers were stable until 96 h and got internalized into RB, WERI-Rb1 and breast cancer, MDAMB453 cell lines. The constructs were studied using the recombinant dicer enzyme for the siRNA generation. Quantitative polymerase chain reaction and immunofluorescence by microscopic analysis of chimeras in vitro exhibited silencing of stathmin and survivin in the RB and breast cancer model. The chimeric constructs showed significant inhibition of cell proliferation of breast cancer cells. Thus, LNA-modified aptamer-based siRNA delivery aids in cell targeting and necessitates further studies in animal ...Continue Reading

References

Jun 26, 2003·Nucleic Acids Research·Michael Zuker
Nov 24, 2004·Investigative Ophthalmology & Visual Science·Subramanian KrishnakumarLifen Ren-Heidenreich
Dec 19, 2006·Molecular Cancer Therapeutics·Christopher R Ireson, Lloyd R Kelland
Mar 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Dan PeerMotomu Shimaoka
Jan 10, 2009·Nature Reviews. Cancer·Olivier GiresPatrick A Baeuerle
Mar 19, 2009·Journal of Cancer Research and Clinical Oncology·Du WenqiFan Daiming
Jun 23, 2009·Stem Cells·Bárbara GonzálezOlivier Gires
Feb 11, 2010·Biochimica Et Biophysica Acta·Erik W OravaJean Gariépy
Oct 1, 2011·Critical Reviews in Biochemistry and Molecular Biology·Jagat R KanwarRupinder K Kanwar
Jun 13, 2012·Expert Opinion on Therapeutic Targets·John Nemunaitis
Dec 20, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hacer GuvencIchiro Nakano
Apr 12, 2013·Cell Biology International·Huiwen HaoXin Xie
Apr 27, 2013·Nucleic Acids Research·Stanislav BellaousovDavid H Mathews
Jun 28, 2013·Pediatric Blood & Cancer·Job SudhakarJyotirmay Biswas
Aug 21, 2013·PloS One·Nithya SubramanianSubramanian Krishnakumar
Jul 1, 2014·Nanomedicine·Evžen AmlerAldo R Boccaccini
Sep 23, 2014·Pathology, Research and Practice·Nevine M F El Deeb, Eman Abdelzaher
Jan 13, 2015·Journal of Biomedical Science·Nithya SubramanianSubramanian Krishnakumar
Mar 24, 2015·Chemical Communications : Chem Comm·Nithya SubramanianSubramanian Krishnakumar
Jul 16, 2015·PloS One·Nithya SubramanianSubramanian Krishnakumar

❮ Previous
Next ❯

Citations

Jun 21, 2016·Journal of Pediatric Hematology/oncology·Jaisy SamuelSubramanian Krishnakumar
Mar 24, 2017·Expert Opinion on Biological Therapy·Giulia BottaiLibero Santarpia
Oct 19, 2017·International Journal of Molecular Sciences·Zhenjian ZhuoBaoting Zhang
Aug 3, 2018·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Padmanaban SivakumarMin Suk Shim
Oct 9, 2018·Current Medicinal Chemistry·Fen HeYanfei Liu
Jul 1, 2020·ACS Applied Materials & Interfaces·Shuaijian NiGe Zhang

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
transfection
electrophoresis
transfections

Software Mentioned

imageJ
Mfold
GraphPad Prism
RNA structure

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Related Papers

Nucleic Acid Therapeutics
Kasper K Karlsen, Jesper Wengel
© 2021 Meta ULC. All rights reserved