Preclinical and clinical development of siRNA-based therapeutics

Gulnihal Ozcan, Bulent Ozpolat, Robert L. Coleman, Anil K. Sood, Gabriel Lopez-Berestein

    Research output: Contribution to journalReview articlepeer-review

    379 Scopus citations


    The discovery of RNA interference, first in plants and Caenorhabditis elegans and later in mammalian cells, led to the emergence of a transformative view in biomedical research. Knowledge of the multiple actions of non-coding RNAs has truly allowed viewing DNA, RNA and proteins in novel ways. Small interfering RNAs (siRNAs) can be used as tools to study single gene function both in vitro and in vivo and are an attractive new class of therapeutics, especially against undruggable targets for the treatment of cancer and other diseases. Despite the potential of siRNAs in cancer therapy, many challenges remain, including rapid degradation, poor cellular uptake and off-target effects. Rational design strategies, selection algorithms, chemical modifications and nanocarriers offer significant opportunities to overcome these challenges. Here, we review the development of siRNAs as therapeutic agents from early design to clinical trial, with special emphasis on the development of EphA2-targeting siRNAs for ovarian cancer treatment.

    Original languageEnglish (US)
    Pages (from-to)108-119
    Number of pages12
    JournalAdvanced Drug Delivery Reviews
    StatePublished - Jun 29 2015


    • EphA2
    • Gene silencing
    • Nanocarriers
    • Nanoliposomes
    • Ovarian cancer
    • SiRNA
    • Therapeutic use

    ASJC Scopus subject areas

    • Pharmaceutical Science


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