Targeting cancer cells using LNA-modified aptamer-siRNA chimeras

Subramanian, Nithya, Kanwar, Jagat R., Kanwar, Rupinder K. and Krishnakumar, Subramanian 2015, Targeting cancer cells using LNA-modified aptamer-siRNA chimeras, Nucleic acid therapeutics, vol. 25, no. 6, pp. 317-322, doi: 10.1089/nat.2015.0550.

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Title Targeting cancer cells using LNA-modified aptamer-siRNA chimeras
Author(s) Subramanian, Nithya
Kanwar, Jagat R.ORCID iD for Kanwar, Jagat R.
Kanwar, Rupinder K.
Krishnakumar, Subramanian
Journal name Nucleic acid therapeutics
Volume number 25
Issue number 6
Start page 317
End page 322
Total pages 6
Publisher Mary Ann Liebert Publishers
Place of publication New Rochelle, N.Y.
Publication date 2015-11-23
ISSN 2159-3345
Summary 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 models.
Language eng
DOI 10.1089/nat.2015.0550
Field of Research 111299 Oncology and Carcinogenesis not elsewhere classified
Socio Economic Objective 920102 Cancer and Related Disorders
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Mary Ann Liebert Publishers
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School of Medicine
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