The Ohio State University

Entrada Therapeutics, Inc.

Ziqing Qian

Dehua Pei

Natarajan Sethuraman

Jason Ruth

George Appiah Kubi

John W Christman

Manjula Karpurapu

Louis A Tartaglia

Lou A Tartaglia

Marina Buyanova

Kyle A Totaro

Disclosed herein are peptides having activity as cell penetrating peptides. In some embodiments, the peptides can comprise a cell penetrating peptide moiety and beta-haripin turn creating moiety. In other embodiments, the peptides also comprise a cargo moiety.

Cyclic cell penetrating peptides comprising beta-hairpin motifs and methods of making and using thereof

Disclosed are compounds that can penetrate the mitochondrial membrane and that are able to deliver cargo (e.g., therapeutic agents) specifically to the mitochondria.

Non-peptidic cell-penetrating motifs

The present disclosure provides the synthesis of phosphorodiamidate morpholino oligomers (PMOs) in high purity, yield, and efficiency from Fmoc-protected morpholino monomers, e.g., Fmoc morpholino monomer G.

Synthesis of FMOC-protected morpholino monomers and oligomers

The present disclosure provides for polypeptide conjugates. The polypeptide conjugates disclosed herein comprise a polyarginine peptide and a cyclic cell-penetrating peptide (cCPP) conjugated, directly or indirectly, to the polyarginine peptide. The present disclosure demonstrates that cCPPs conjugated to polyarginine peptides can be used to deliver nucleic acids to the cytosol of cells.

Polypeptide conjugates for intracellular delivery of nucleic acids

Disclosed herein are compositions and methods of treating disclosure provides for compounds for use in treating Mitochondrial Neurogastrointestinal Encephalopathy Syndrome (MNGIE). In some embodiments, the compounds have cell penetrating activity and thymidine phosphorylase activity. In certain embodiments, the compounds disclosed herein comprise: a) at least one cell-penetrating peptide (CPP) moiety; and b) a thymidine phosphorylase, or an active fragment or analog thereof (TP), wherein the CPP is coupled, directly or indirectly, to TP.

Compositions and methods for treating mitochondrial neurogastrointestinal encephalopathy

Disclosed is a general, reversible bicyclization strategy to increase both the proteolytic stability and cell permeability of peptidyl drugs. A peptide drug is fused with a short cell-penetrating motif and converted into a conformationally constrained bicyclic structure through the formation of a pair of disulfide bonds. The resulting bicyclic peptide has greatly enhanced proteolytic stability as well as cell-permeability. Once inside the cell, the disulfide bonds are reduced to produce a linear, biologically active peptide. This strategy was applied to generate a cell-permeable bicyclic peptidyl inhibitor against the NEMO-IKK interaction.

Di-sulfide containing cell penetrating peptides and methods of making and using thereof

Disclosed herein are peptides having activity as cell penetrating peptides. In some embodiments, the peptides can comprise a cell penetrating peptide moiety and beta-hairpin turn creating moiety. In other embodiments, the peptides also comprise a cargo moiety.

Disclosed herein are compounds having activity as cell penetrating peptides. In some examples, the compounds can comprise a cell penetrating peptide moiety and a cargo moiety. The cargo moiety can comprise one or more detectable moieties, one or more therapeutic moieties, one or more targeting moieties, or any combination thereof. In some examples, the cell penetrating peptide moiety is cyclic. In some examples, the cell penetrating peptide moiety and cargo moiety together are cyclic. In some examples, the cell penetrating peptide moiety is cyclic and the cargo moiety is appended to the cyclic cell penetrating peptide moiety structure. In some examples, the cargo moiety is cyclic and the cell penetrating peptide moiety is cyclic, and together they form a fused bicyclic system.

Cell penetrating peptides and methods of making and using thereof

Improved calcineurin inhibitors and methods of using these improved calcineurin inhibitors to inhibit calcineurin-NFAT signaling in cells and in subjects are disclosed.

Growing community of inventors

Columbus, OH, United States of America

Ziqing Qian