Progress in the development of nucleic acid therapeutics for cancer

Anna Kalota1, Susan E Shetzline, Alan M Gewirtz

  • 1Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.

Cancer Biology & Therapy
|January 17, 2004
PubMed

Insights

Gene silencing agents offer targeted cancer therapy by inhibiting abnormal gene expression. This review focuses on messenger RNA (mRNA) targeting strategies like antisense oligonucleotides (ODN) and short interfering RNA (siRNA) for potential clinical use.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Aberrant gene expression is a hallmark of many cancers.
  • Targeted gene silencing offers a potentially less toxic alternative to conventional chemotherapy.
  • Several strategies exist to inhibit gene expression at transcriptional or translational levels.

Purpose of the Study:

  • To review gene silencing agents for cancer therapeutics.
  • To focus on messenger RNA (mRNA) targeting methodologies.
  • To address challenges in clinical application, including cellular delivery and targeting efficacy.

Main Methods:

  • Overview of gene silencing strategies, including triple helix forming oligonucleotides, decoy transcription factor binding oligonucleotides, antisense oligonucleotides (ODN), and short interfering RNA (siRNA).
  • Focus on mRNA targeting agents.
  • Discussion of clinical considerations for nucleic acid-based therapeutics.

Main Results:

  • Various nucleic acid-based agents target gene expression at transcription or mRNA translation.
  • Antisense ODN and siRNA are key mRNA targeting modalities.
  • Cellular delivery and successful targeting are critical for clinical success.

Conclusions:

  • Gene silencing agents, particularly mRNA-targeting ones, show therapeutic promise for cancer.
  • Further development is needed to overcome challenges in delivery and targeting for clinical translation.
  • Nucleic acid-based therapeutics represent a potential new frontier in cancer treatment.

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