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Degradable Terpolymers with Alkyl Side Chains Demonstrate Enhanced Gene Delivery Potency and Nanoparticle Stability

Authors

  • Ahmed A. Eltoukhy,

    1. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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  • Delai Chen,

    1. David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    2. Department of Anesthesiology, Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA
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  • Christopher A. Alabi,

    1. David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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  • Robert Langer,

    1. Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    2. David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    3. Department of Chemical Engineering and Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
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  • Daniel G. Anderson

    Corresponding author
    1. David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    2. Department of Chemical Engineering and Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    • David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
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Abstract

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Degradable, cationic poly(β-amino ester)s (PBAEs) with alkyl side chains are developed for non-viral gene delivery. Nanoparticles formed from these PBAE terpolymers exhibit significantly enhanced DNA transfection potency and resistance to aggregation. These hydrophobic PBAE terpolymers, but not PBAEs lacking alkyl side chains, support interaction with PEG-lipid conjugates, facilitating their functionalization with shielding and targeting moieties and accelerating the in vivo translation of these materials.

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