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    UNIVERSAL MULTI-FUNCTIONAL GSH-RESPONSIVE SILICA NANOPARTICLES FOR DELIVERY OF BIOMOLECULES INTO CELLS
    3.
    发明申请
    UNIVERSAL MULTI-FUNCTIONAL GSH-RESPONSIVE SILICA NANOPARTICLES FOR DELIVERY OF BIOMOLECULES INTO CELLS 有权

    公开(公告)号：US20220105202A1

    公开(公告)日：2022-04-07

    申请号：US17501635

    申请日：2021-10-14

    Applicant: Wisconsin Alumni Research Foundation

    Inventor： Shaoqin GONG ,  Yuyuan Wang

    IPC: A61K48/00 ,  A61K9/51 ,  A61K47/69 ,  A61P25/00 ,  C08G83/00

    Abstract: The present technology provides a nanoparticle comprising: the polysiloxanes comprise silyloxy subunits having the structure (I) as shown herein, wherein Ra at each occurrence is independently selected from a bond to a Si of another polysiloxane chain or a C1-12 alkyl group; Ri at each occurrence is independently selected from the group consisting of C1-12 alkyl and C2-12 alkenyl groups, optionally substituted with a substituent selected from the group consisting of halogen and NR12, wherein each occurrence of R1 is independently selected from H or a C1-12 alkyl group, or two R1 groups, together with the N atom to which they are attached, form a pyrrolidine or piperidine ring; the crosslinks between polysiloxanes comprise disulfide linkages, the nanoparticle comprises an exterior surface comprising surface-modifying groups attached to and surrounding the silica network, wherein the surface-modifying groups comprise polyethylene glycol (PEG), polysarcosine, polyzwitterion, polycation, polyanion, or combinations of two or more thereof; and the nanoparticle has an average diameter of 15 nm to 200 nm. The nanoparticles herein may include biomolecules such as polynucleic acids, proteins, and complexes thereof, e.g., Cas9 RNP.

    Polyplex delivery system for proteins, nucleic acids and protein/nucleic acid complexes
    5.
    发明授权
    Polyplex delivery system for proteins, nucleic acids and protein/nucleic acid complexes 有权

    公开(公告)号：US11351263B2

    公开(公告)日：2022-06-07

    申请号：US16282174

    申请日：2019-02-21

    Applicant: Wisconsin Alumni Research Foundation

    Inventor： Shaoqin Gong ,  Yuyuan Wang ,  Krishanu Saha ,  Amr Ashraf Abdeen

    IPC: A61K9/00 ,  A61K47/59 ,  A61K47/61 ,  A61K31/7105 ,  A61K51/06 ,  A61K38/46 ,  A61K49/00

    Abstract: Provided herein are nanoplexes comprising a payload selected from a protein and/or a polynucleic acid; and a plurality of copolymers comprising a first copolymer that is poly(N,N′-bis(acryloyl)cystamine-poly(aminoalkyl)) (PBAP), a second copolymer that is poly(C2-3 akylene glycol)-PBAP-poly(C2-3 akylene glycol), and a third copolymer that is TG-poly(C2-3 akylene glycol)-PBAP-poly(C2-3 akylene glycol)-TG wherein TG at each occurrence is independently a targeting ligand, a cell penetrating peptide, an imaging agent or a capping group, provided that a plurality of TG groups is a targeting ligand; wherein the payload is non-covalently complexed to one or more of the copolymers, one or more of the first, second, and/or third copolymers comprises an endosomal escape group having a pKa of about 4.5 to about 6.5, and optionally one or more of the first, second, and/or third copolymers comprises a host and a guest non-covalent crosslinker.

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