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Poly(Lactic-co-Glycolic Acid) Nanoparticle Delivery of Peptide Nucleic Acids In Vivo

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Book cover Peptide Nucleic Acids

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2105))

Abstract

Many important biological applications of peptide nucleic acids (PNAs) target nucleic acid binding in eukaryotic cells, which requires PNA translocation across at least one membrane barrier. The delivery challenge is further exacerbated for applications in whole organisms, where clearance mechanisms rapidly deplete and/or deactivate exogenous agents. We have demonstrated that nanoparticles (NPs) composed of biodegradable polymers can encapsulate and release PNAs (alone or with co-reagents) in amounts sufficient to mediate desired effects in vitro and in vivo without deleterious reactions in the recipient cell or organism. For example, poly(lactic-co-glycolic acid) (PLGA) NPs can encapsulate and deliver PNAs and accompanying reagents to mediate gene editing outcomes in cells and animals, or PNAs alone to target oncogenic drivers in cells and correct cancer phenotypes in animal models. In this chapter, we provide a primer on PNA-induced gene editing and microRNA targeting—the two PNA-based biotechnological applications where NPs have enhanced and/or enabled in vivo demonstrations—as well as an introduction to the PLGA material and detailed protocols for formulation and robust characterization of PNA/DNA-laden PLGA NPs.

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Acknowledgments

This work was supported by the NIGMS Medical Scientist Training Program T32GM07205 (to E.Q.); National Institutes of Health grants R01HL125892, R01AI112443, and UG3HL147352 (to W.M.S. and P.M.G.); and institutional training grant 5T32GM007223-43 (to E.Q.). A.S.P. was supported by NIH National Research Service Awards (NRSAs): T32 (GM86287) training grant and F32 (HL142144) individual postdoctoral fellowship. S.N.O was supported by UG3HL147352 (to P.M.G. and W.M.S.).

Disclosures/Competing interests: E.Q., A.S.P., W.M.S., and P.M.G. are consultants for Trucode Gene Repair, Inc. W.M.S. and P.M.G also have equity interests in Trucode Gene Repair, Inc.

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Authors and Affiliations

  1. Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, USA

    Stanley N. Oyaghire & Peter M. Glazer

  2. Department of Genetics, Yale University School of Medicine, New Haven, CT, USA

    Elias Quijano

  3. Department of Biomedical Engineering, Yale University, New Haven, CT, USA

    Alexandra S. Piotrowski-Daspit & W. Mark Saltzman

  4. Department of Chemical & Environmental Engineering, Yale University, New Haven, CT, USA

    W. Mark Saltzman

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  1. Stanley N. Oyaghire
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  2. Elias Quijano
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  3. Alexandra S. Piotrowski-Daspit
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  4. W. Mark Saltzman
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  5. Peter M. Glazer
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Corresponding author

Correspondence to Peter M. Glazer .

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Editors and Affiliations

  1. Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Peter E. Nielsen

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Oyaghire, S.N., Quijano, E., Piotrowski-Daspit, A.S., Saltzman, W.M., Glazer, P.M. (2020). Poly(Lactic-co-Glycolic Acid) Nanoparticle Delivery of Peptide Nucleic Acids In Vivo. In: Nielsen, P. (eds) Peptide Nucleic Acids. Methods in Molecular Biology, vol 2105. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0243-0_17

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  • DOI: https://doi.org/10.1007/978-1-0716-0243-0_17

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0242-3

  • Online ISBN: 978-1-0716-0243-0

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