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Membrane-lytic block copolymers

A technology of block copolymers and drugs, which can be applied in the direction of drug combination, drug delivery, peptide/protein components, etc., and can solve the problems of difficult translation and in vivo application

Inactive Publication Date: 2019-04-26
UNIV OF WASHINGTON
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

These methods generally work well in cultured cells, but may not be easily translated for in vivo applications

Method used

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  • Membrane-lytic block copolymers
  • Membrane-lytic block copolymers
  • Membrane-lytic block copolymers

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Embodiment

[0283] Design of a self-assembling synthetic polymer containing a hidden membrane-lytic peptide at neutral pH. This polymer undergoes a conformational change in acidic environments such as early endosomes to reveal peptides for selective endosomal membrane disruption. The peptide employed was melittin which can insert into lipid membranes and induce pore formation. M.T. Tosteson et al. Biophysical Journal, 36, 109-116. Melittin has been conjugated to various cationic polymers and has been shown to enhance gene transfer capability by promoting endosomal release of the vector. M. Ogris et al. Journal of Biological Chemistry 2001, 276, 47550-47555.

[0284] A melittin-containing polymer, VIPER, has been shown to have selective membrane lysis at acidic pH. VIPER efficiently packages plasmid DNA for delivery into various mammalian cells with a higher efficiency than commercial agents. Finally, it was shown that VIPER can be used for efficient in vivo gene transfer into tumors, ...

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Abstract

Membrane-lytic block copolymers, miceliar assemblies, pharmaceutical compositions, and related methods are described.

Description

[0001] Statement Regarding Federally Sponsored Research [0002] This invention was made with government support under Grant No. R01NS064404 awarded by the National Institutes of Health. The government has certain rights in this invention. Background technique [0003] The potentially transformative impact of intracellular drugs such as nucleic acid-based drugs, peptides, and proteins has not been clinically realized primarily due to the considerable delivery challenges involved in the intracellular delivery of macromolecular therapeutics. M.E. Davis et al. Nature 2010, 464, 1067-U1140; b) M.A. Kay, Nat Rev Genet 2011, 12, 316-328; c) K.A. Whitehead et al. Nat Rev Drug Discov 2009, 8, 129-138. For nucleic acids, two main classes of delivery vehicles, viral systems and non-viral systems, are used to package cargo and facilitate cellular uptake, but with their corresponding limitations. Viral vectors have immunogenicity and health concerns and are expensive to manufacture. C....

Claims

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Application Information

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IPC IPC(8): A61K49/00A61K47/34A61K47/50A61K47/55A61K47/56
CPCA61K47/58A61K47/6907A61K38/10A61K38/1761A61P35/00C08L33/12
Inventor 成一龙S·H·潘
Owner UNIV OF WASHINGTON
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