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Peptide carriers to the rescue: overcoming the barriers to siRNA delivery for cancer treatment

  • Author Footnotes
    1 Both authors contributed equally to this work.
    James C. Cummings
    Footnotes
    1 Both authors contributed equally to this work.
    Affiliations
    Departments of Oral Health Sciences and Biochemistry & Molecular Biology, Hollings Cancer Center, Medical University of South Carolina (MUSC), Charleston, South Carolina
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  • Author Footnotes
    1 Both authors contributed equally to this work.
    Haiwen Zhang
    Footnotes
    1 Both authors contributed equally to this work.
    Affiliations
    Departments of Oral Health Sciences and Biochemistry & Molecular Biology, Hollings Cancer Center, Medical University of South Carolina (MUSC), Charleston, South Carolina
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  • Andrew Jakymiw
    Correspondence
    Reprint requests: Andrew Jakymiw, Departments of Oral Health Sciences and Biochemistry & Molecular Biology, Hollings Cancer Center, MUSC, 173 Ashley Avenue, MSC 507, Charleston, SC 29425.
    Affiliations
    Departments of Oral Health Sciences and Biochemistry & Molecular Biology, Hollings Cancer Center, Medical University of South Carolina (MUSC), Charleston, South Carolina
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  • Author Footnotes
    1 Both authors contributed equally to this work.
      Cancer is a significant health concern worldwide and its clinical treatment presents many challenges. Consequently, much research effort has focused on the development of new anticancer drugs to combat this disease. One area of exploration, in particular, has been in the therapeutic application of RNA interference (RNAi). Although RNAi appears to be an attractive therapeutic tool for the treatment of cancer, one of the primary obstacles towards its pervasive use in the clinic has been cell/tissue type-specific cytosolic delivery of therapeutic small interfering RNA (siRNA) molecules. Consequently, varied drug delivery platforms have been developed and widely explored for siRNA delivery. Among these candidate drug delivery systems, peptides have shown great promise as siRNA carriers due to their varied physiochemical properties and functions, simple formulations, and flexibility in design. In this review, we will focus on distinguishing between the different classes of peptide carriers based on their functions, as well as summarize and discuss the various design strategies and advancements that have been made in circumventing the barriers to siRNA delivery for cancer treatment. Resolution of these challenges by peptide carriers will accelerate the translation of RNAi-based therapies to the clinic.

      Abbreviations:

      CPPs (cell-penetrating peptides), dsRBD (double-stranded RNA binding domain), EGFR (epidermal growth factor receptor), I4R (interleukin-4 receptor), PEG (poly[ethylene glycol]), RISC (RNA-induced silencing complex), RNAi (RNA interference), siRNA (small interfering RNA), Ssb (Sjögren's syndrome antigen B)
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