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Water-Soluble Cationic Methacrylate Polymers for Nonviral Gene Delivery

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Nonviral Vectors for Gene Therapy

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 65))

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Abstract

The aim of gene therapy is to treat inherited or acquired genetic deficiencies (e.g., cystic fibrosis) or viral diseases (e.g., hepatitis B, HIV) by introduction of DNA encoding a therapeutic protein or a specific virus antigen, respectively, into the nucleus of the target cell. Because naked DNA will barely pass cellular membranes, a carrier system is required for transfection (1–4). Cationic polymers, which condense DNA by ionic interaction, form a promising class of nonviral transfection agents. Well-known examples of these polymers are DEAE dextran, poly(L-lysine), poly(ethylenimine), and poly(2- [dimethylamino]ethyl methacrylate) (pDMAEMA) (5–10). In order to achieve transfection, aplasmid must be delivered into the nucleus, which requires cellular uptake of polymerDNA complexes, generally referred to as “polyplexes” (11), which most likely occurs via endocytosis, followed by endosomal escape and transport to the nucleus. The polyplex must dissociate, either in the cytosol or in the nucleus, which may be a critical step in the transfection process.

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Author information

Authors and Affiliations

  1. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht

    Gert W. Bos

  2. OctoPlus B. V., Leiden, Netherlands

    Daan J. A. Crommelin

  3. Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht, Netherlands

    Wim E. Hennink

Authors
  1. Gert W. Bos
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  2. Daan J. A. Crommelin
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  3. Wim E. Hennink
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Editor information

Editors and Affiliations

  1. Praecis Pharmaceuticals Incorporated, Waltham, MA

    Mark A. Findeis

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© 2001 Humana Press Inc.

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Bos, G.W., Crommelin, D.J.A., Hennink, W.E. (2001). Water-Soluble Cationic Methacrylate Polymers for Nonviral Gene Delivery. In: Findeis, M.A. (eds) Nonviral Vectors for Gene Therapy. Methods in Molecular Medicine™, vol 65. Humana Press. https://doi.org/10.1385/1-59259-139-6:35

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  • DOI: https://doi.org/10.1385/1-59259-139-6:35

  • Publisher Name: Humana Press

  • Print ISBN: 978-0-89603-712-0

  • Online ISBN: 978-1-59259-139-8

  • eBook Packages: Springer Protocols

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