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• W2891692346 abstract "Gene therapy holds great promise for the treatment of many diseases, but clinical translation of gene therapies has been slowed down by the lack of safe and efficient gene delivery systems. Here, we report two versatile redox-responsive polyplexes (i.e., cross-linked and non-crosslinked) capable of efficiently delivering a variety of negatively charged payloads including plasmid DNA (DNA), messenger RNA, Cas9/sgRNA ribonucleoprotein (RNP), and RNP–donor DNA complexes (S1mplex) without any detectable cytotoxicity. The key component of both types of polyplexes is a cationic poly(N,N′-bis(acryloyl)cystamine-co-triethylenetetramine) polymer [a type of poly(N,N′-bis(acryloyl)cystamine–poly(aminoalkyl)) (PBAP) polymer] containing disulfide bonds in the backbone and bearing imidazole groups. This composition enables efficient encapsulation, cellular uptake, controlled endo/lysosomal escape, and cytosolic unpacking of negatively charged payloads. To further enhance the stability of non-crosslinked PBAP polyplexes, adamantane (AD) and β-cyclodextrin (β-CD) were conjugated to the PBAP-based polymers. The cross-linked PBAP polyplexes formed by host–guest interaction between β-CD and AD were more stable than non-crosslinked PBAP polyplexes in the presence of polyanionic polymers such as serum albumin, suggesting enhanced stability in physiological conditions. Both cross-linked and non-crosslinked polyplexes demonstrated either similar or better transfection and genome-editing efficiencies, and significantly better biocompatibility than Lipofectamine 2000, a commercially available state-of-the-art transfection agent that exhibits cytotoxicity." @default.
• W2891692346 created "2018-09-27" @default.
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• W2891692346 date "2018-09-17" @default.
• W2891692346 modified "2023-10-11" @default.
• W2891692346 title "Versatile Redox-Responsive Polyplexes for the Delivery of Plasmid DNA, Messenger RNA, and CRISPR-Cas9 Genome-Editing Machinery" @default.
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• W2891692346 doi "https://doi.org/10.1021/acsami.8b09642" @default.
• W2891692346 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6530788" @default.
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