The invention provides processes of purifying a peptide including a GCC agonist sequence selected from the group consisting of SEQ ID NOs: 1-251 described herein. The processes include a solvent exchange step before a freeze-drying (lyophilization) step.

The present application provides materials and methods for treating a patient with autosomal dominant CORD, both ex vivo and in vivo; materials and methods for editing a GUCY2D gene in a human cell; and materials and methods for editing a R838H, R838C, or R838S mutation in a GUCY2D gene in a human cell. The present application also provides one or more gRNAs or sgRNAs for editing a GUCY2D gene; one or more gRNAs or sgRNAs for editing a R838H, R838C, or R838S mutation in a GUCY2D gene; and a therapeutic comprising at least one or more gRNAs or sgRNAs for editing a R838H, R838C, or R838S mutation in a GUCY2D gene. The present application provides a therapeutic for treating a patient with autosomal dominant CORD. The present application also provides a kit for treating a patient with autosomal dominant CORD. In addition, the present application provides a self-inactivating CRISPR-Cas system.

The invention provides processes of purifying a peptide including a GCC agonist sequence selected from the group consisting of SEQ ID NOs: 1-251 described herein. The processes include a solvent exchange step before a freeze-drying (lyophilization) step.

The invention provides low-dose formulations of guanylate cyclase-C (“GCC”) agonist peptides and methods for their use. The formulations of the invention can be administered either alone or in combination with one or more additional therapeutic agents, preferably an inhibitor of cGMP-dependent phosphodiesterase or a laxative.

Embodiments disclosed herein provide compositions for conjugates, including fusion proteins, and methods of using them to treat a variety of conditions. In some embodiments, the conjugates and/or fusion proteins incorporate a 60-amino acid human homeodomain (e.g., peptides derived from human HOX genes), to translocate functional and regulatory peptides and proteins or other biologically active molecules such as nucleic acids, which are not naturally associated with the human homeodomain, across cell and nuclear membranes to intended sites of action without provoking an unwanted immune response that may reduce exposure to the conjugate and/or result in a clinical adverse event. In further embodiments, disclosed conjugates and fusion proteins can pass through the blood-brain barrier to allow entry into the CNS. In various embodiments, the disclosed compositions are suitable for delivery into a cell (i) the expression product of a gene of interest and/or (ii) novel peptides or polynucleotides to regulate gene function.

According to the invention, gene products expressed in a tumor-associated manner and the nucleic acids coding therefor were identified. The invention relates to the therapy and diagnosis of diseases wherein said gene products expressed in a tumor-associated manner are aberrantly expressed. The invention also relates to proteins, polypeptides and peptides which are expressed in a tumor associated manner and to nucleic acids coding therefor.

Embodiments disclosed herein provide compositions for conjugates, including fusion proteins, and methods of using them to treat a variety of conditions. In some embodiments, the conjugates and/or fusion proteins incorporate a 60-amino acid human homeodomain (e.g., peptides derived from human HOX genes), to translocate functional and regulatory peptides and proteins or other biologically active molecules such as nucleic acids, which are not naturally associated with the human homeodomain, across cell and nuclear membranes to intended sites of action without provoking an unwanted immune response that may reduce exposure to the conjugate and/or result in a clinical adverse event. In further embodiments, disclosed conjugates and fusion proteins can pass through the blood-brain barrier to allow entry into the CNS. In various embodiments, the disclosed compositions are suitable for delivery into a cell (i) the expression product of a gene of interest and/or (ii) novel peptides or polynucleotides to regulate gene function.

The invention provides processes of purifying a peptide including a GCC agonist sequence selected from the group consisting of SEQ ID NOs: 1-251 described herein. The processes include a solvent exchange step before a freeze-drying (lyophilization) step.

The invention provides low-dose formulations of guanylate cyclase-C (GCC) agonist peptides and methods for their use. The formulations of the invention can be administered either alone or in combination with one or more additional therapeutic agents, preferably an inhibitor of cGMP-dependent phosphodiesterase or a laxative.

The present application provides materials and methods for treating a patient with autosomal dominant CORD, both ex vivo and in vivo; materials and methods for editing a GUCY2D gene in a human cell; and materials and methods for editing a R838H, R838C, or R838S mutation in a GUCY2D gene in a human cell. The present application also provides one or more gRNAs or sgRNAs for editing a GUCY2D gene; one or more gRNAs or sgRNAs for editing a R838H, R838C, or R838S mutation in a GUCY2D gene; and a therapeutic comprising at least one or more gRNAs or sgRNAs for editing a R838H, R838C, or R838S mutation in a GUCY2D gene. The present application provides a therapeutic for treating a patient with autosomal dominant CORD. The present application also provides a kit for treating a patient with autosomal dominant CORD. In addition, the present application provides a self-inactivating CRISPR-Cas system.