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Updated: Aug 14, 2026

Methods to Discover Alternative Promoter Usage and Transcriptional Regulation of Murine Bcrp1
11:02

Methods to Discover Alternative Promoter Usage and Transcriptional Regulation of Murine Bcrp1

Published on: May 27, 2016

Selection and characterization of a high-activity ribozyme directed against the antineoplastic drug

P Kowalski1, A Wichert, P S Holm

  • 1Institute of Pathology, Humboldt University Berlin, Germany.

Cancer Gene Therapy
|May 3, 2001
PubMed

Insights

Researchers designed hammerhead ribozymes to target breast cancer resistance protein (BCRP) mRNA. One ribozyme effectively cleaved BCRP mRNA, offering potential for reversing multidrug resistance in cancer.

Area of Science:

  • Molecular Biology
  • Biochemistry
  • Genetics

Background:

  • Breast cancer resistance protein (BCRP) is an ATP-binding cassette transporter.
  • Overexpression of BCRP is linked to multidrug resistance in various cancer cell lines.
  • BCRP is a potential target for overcoming drug resistance phenotypes.

Purpose of the Study:

  • To design and test hammerhead ribozymes for cleaving BCRP-encoding mRNA.
  • To identify a ribozyme with high activity against BCRP mRNA.
  • To explore the potential of ribozymes in reversing BCRP-mediated drug resistance.

Main Methods:

  • Design and in vitro synthesis of six hammerhead ribozymes targeting BCRP mRNA.
  • Generation of BCRP-encoding substrate RNA using RT-PCR from multidrug-resistant cells.
  • Assessment of ribozyme cleavage activity at physiologic conditions.

Main Results:

  • One anti-BCRP ribozyme demonstrated significant endoribonucleolytic cleavage activity.
  • The active ribozyme was characterized for kinetic parameters in a cell-free system.
  • High BCRP mRNA expression was observed in the EPG85-257RNOV cell line.

Conclusions:

  • A specific hammerhead ribozyme effectively cleaves BCRP mRNA.
  • This ribozyme holds promise as a therapeutic tool for overcoming BCRP-mediated multidrug resistance.
  • Further characterization and in vivo studies are warranted.

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