Charge Conversional Ternary Polyplex
Disclosed is a polymer composite (polyplex) that contains nucleic acid, a cationic polymer, and an anionic polymer. The anionic polymer covers the surface of the composite comprising the cationic polymer and nucleic acid, has a negative charge at neutral pH, and can change so as to have a positive charge at mildly acidic pH.
The present invention relates to a polymer complex (polyplex) containing a nucleic acid for use as a nonviral synthetic vector capable of delivering the nucleic acid to a target cell. More particularly, the present invention relates to a charge conversional ternary polyplex comprising a nucleic acid, a cationic polymer and an anionic polymer, wherein the anionic polymer covers the surface of a complex comprising the cationic polymer and the nucleic acid.
The present inventors have examined a new approach for a polyplex design that exerts both properties of high transfection activity and low toxicity by integrating a charge conversional moiety into a polyplex structure. Although maleic acid amide derivatives, i.e., cis-aconitic acid amide and citraconic acid amide, bear negative charges at neutral pH, they are rapidly degraded at weak acidity of pH 5.5 and expose the positively-charged amine<>. Therefore, a ternary polyplcx (a polyplex having pDNA/polycation/polyanion having degrading side-chain) formed by the present inventors by covering the surface of a positively-charged polyplex with a polymer derived from degrading amide, by which the ternary polymer maintains neutrally- to negatively-charged properties outside the cell. On the other hand, in the acidic environment of endosomes, the charge conversional moieties are expected to charge positively and promote endosomal escape of the polyplex owing to membrane disruption.
KATAOKA KAZUNORI [JP]; LEE YAN [JP]; NISHIYAMA NOBUHIRO [JP]; MIYATA KANJIRO [JP]; OBA MAKOTO [JP]; HIKI SHIGEHIRO [JP]; SANJO M
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