Wisconsin Alumni Research Foundation

Yuyuan Wang

Shaoqin Gong

Krishanu Saha

Amr Ashraf Abdeen

Wei Xu

Fabao Liu

Guojun Chen

Ruosen Xie

Provided herein are peptides comprising an amino acid sequence having at least about 85% sequence identity to RYRPRAPIIAVT (SEQ ID NO: 1). These cationic peptides inhibit PKM2 methylation and may be used in the treatment of breast cancer and other diseases or conditions in which PKM2 is overexpressed. Such PKM2 peptides may be delivered to cancer cells using pH sensitive unimolecular nanoparticles comprising anionic polymers.

Therapeutic cationic peptides and unimolecular nanoparticles for efficient delivery thereof

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(Cakylene glycol)-PBAP-poly(Cakylene glycol), and a third copolymer that is TG-poly(Cakylene glycol)-PBAP-poly(Cakylene 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.

Polyplex delivery system for proteins, nucleic acids and protein/nucleic acid complexes

Provided herein are nanocapsules comprising a single ribonucleoprotein (RNP) complex as a core and an biodegradable crosslinked polymer shell that encapsulates the core, wherein the RNP complex comprises a Cas9 polypeptide and a guide RNA, and the biodegradable crosslinked polymer shell comprises polymerized monomers of imidazolyl acryloyl monomers, bisacryloyl disulfide monomers (a biodegradable cross-linker), optionally PEG acryloyl monomers, and either cationic acryloyl monomers, anionic acryloyl monomers, or both cationic and anionic acryloyl monomers (optionally in combination with non-ionic acryloyl monomers) as defined herein. Also provided are methods of making the nanocapsules, kits containing the nanocapsules and methods of delivering the encapsulated RNP to cells.

Nanocapsule delivery system for ribonucleoproteins

Growing community of inventors

Madison, WI, United States of America

Yuyuan Wang