Abstract: Disclosures herein are directed to compositions and methods for increasing gamma globinexpression in a cell or subject by suppressing expression of Klf1. Also described are methods of treating or ameliorating-hemoglobinopathies. The compositions are administered to a subject as a therapeutic amount of a gene editing composition, including an RNA-guided endonuclease and one or more gRNA or sgRNA, or one or more transcription activator-like effector nucleases (TALENs), that targets an intron of a Klf1 gene locus in at least one cell in the subject to effect a deletion in intron, thereby reducing expression of Klf1.

Abstract: The present invention relates to an ecPNA having the general structure: H2N—X—B—Y—COOH and uses thereof, wherein X is A or C and Y is A or C with the proviso that when X is A, Y is C, and when X is C, Y is A; A represents an oligopeptide structure, the sequence of which comprises a sequence which renders the compound able to enter the nucleus of a cell; B represents a peptide nucleic acid (PNA) structure at least 12 nucleotides in length, the sequence of which is capable of hybridizing with a DNA within the nucleus of the cell, which DNA is within a promoter region of a gene; C represents an oligopeptide structure; and each — represents a chemical linkage between the structures at each side thereof, which may be the same as or different from each other such linkage. The ecPNAs provided herein can upregulate or repress gene transcription and are useful for treating diseases requiring changes in transcription and for induction of inducible pluripotent stem (iPS) cells.

Abstract: The present invention relates to an ecPNA having the general structure: H2N—X—B—Y—COOH and uses thereof, wherein X is A or C and Y is A or C with the proviso that when X is A, Y is C, and when X is C, Y is A; A represents an oligopeptide structure, the sequence of which comprises a sequence which renders the compound able to enter the nucleus of a cell; B represents a peptide nucleic acid (PNA) structure at least 12 nucleotides in length, the sequence of which is capable of hybridizing with a DNA within the nucleus of the cell, which DNA is within a promoter region of a gene; C represents an oligopeptide structure; and each — represents a chemical linkage between the structures at each side thereof, which may be the same as or different from each other such linkage.

Abstract: The present invention relates to an ecPNA having the general structure: H2N—X—B—Y—COOH and uses thereof, wherein X is A or C and Y is A or C with the proviso that when X is A, Y is C, and when X is C, Y is A; A represents an oligopeptide structure, the sequence of which comprises a sequence which renders the compound able to enter the nucleus of a cell; B represents a peptide nucleic acid (PNA) structure at least 12 nucleotides in length, the sequence of which is capable of hybridizing with a DNA within the nucleus of the cell, which DNA is within a promoter region of a gene; C represents an oligopeptide structure; and each — represents a chemical linkage between the structures at each side thereof, which may be the same as or different from each other such linkage.