Abstract: A nucleic acid molecule is uniquely designed and encodes an entire CRISPRi or CRISPRa system, while being sized for packaging within a single adeno-associated virus (AAV) vector. Examples of the nucleic acid molecule include about 4600 to 4700 base pairs. Examples of the nucleic acid molecule can include a nucleotide encoding a Cas polypeptide; a nucleotide encoding a repressor or an activator domain attached to the nucleotide encoding the Cas polypeptide via a linker; a first promoter operably connected to the nucleotide encoding the repressor or activator domain or the nucleotide encoding the Cas polypeptide; a nucleotide encoding an alpha-helical connecting the nucleotide encoding the Cas polypeptide to a nuclear localization signal (NLS); and a second promoter operably connected to a guide RNA (gRNA).

Abstract: A promoter for modulating expression of a target gene from a vector includes an enhancer portion comprising the nucleotide sequence of SEQ ID NO: 1 or its complement; a core promoter portion, containing an RNA polymerase binding site, a TATA box, and a transcription start site; and a linker disposed between the enhancer portion and the core promoter portion, containing a restriction site.

Abstract: A nucleic acid molecule is uniquely designed and encodes an entire CRISPRi or CRISPRa system, while being sized for packaging within a single adeno-associated virus (AAV) vector. Examples of the nucleic acid molecule include about 4600 to 4700 base pairs. Examples of the nucleic acid molecule can include a nucleotide encoding a Cas polypeptide; a nucleotide encoding a repressor or an activator domain attached to the nucleotide encoding the Cas polypeptide via a linker; a first promoter operably connected to the nucleotide encoding the repressor or activator domain or the nucleotide encoding the Cas polypeptide; a nucleotide encoding an alpha-helical connecting the nucleotide encoding the Cas polypeptide to a nuclear localization signal (NLS); and a second promoter operably connected to a guide RNA (gRNA).

Abstract: Disclosed are isolated mutant erythropoietin (EPO) polypeptides, functional fragment thereof, nucleic acid encoding such peptides, vectors including such nucleic acids and compositions including such peptides and nucleic acids. The mutant EPO peptides are unique in that they include a substitution at amino acid position number 76, such as a glutamic acid for arginine substation at position 76. This substitution inhibits erythropoietic activity while retaining their neuroprotection. Also disclosed are methods of treating or inhibiting neuronal degeneration, reducing or inhibiting one or more symptoms associated with neuronal degeneration and/or glaucoma in a subject. The methods include administering a therapeutically effective amount of a isolated mutant erythropoietin EPO polypeptide, an expression vector encoding such a mutant erythropoietin EPO polypeptide, a viral particle including an expression vector, or a composition, thereby treating or inhibiting neuronal degeneration in the subject.

Abstract: Disclosed are isolated mutant erythropoietin (EPO) polypeptides, functional fragment thereof, nucleic acid encoding such peptides, vectors including such nucleic acids and compositions including such peptides and nucleic acids. The mutant EPO peptides are unique in that they include a substitution at amino acid position number 76, such as a glutamic acid for arginine substation at position 76. This substitution inhibits erythropoietic activity while retaining their neuroprotection. Also disclosed are methods of treating or inhibiting neuronal degeneration, reducing or inhibiting one or more symptoms associated with neuronal degeneration and/or glaucoma in a subject. The methods include administering a therapeutically effective amount of a isolated mutant erythropoietin EPO polypeptide, an expression vector encoding such a mutant erythropoietin EPO polypeptide, a viral particle including an expression vector, or a composition, thereby treating or inhibiting neuronal degeneration in the subject.

Abstract: Disclosed are isolated mutant erythropoietin (EPO) polypeptides, functional fragment thereof, nucleic acid encoding such peptides, vectors including such nucleic acids and compositions including such peptides and nucleic acids. The mutant EPO peptides are unique in that they include a substitution at amino acid position number 76, such as a glutamic acid for arginine substitution at position 76. This substitution inhibits erythropoietic activity while retaining their neuroprotection. Also disclosed are methods of treating or inhibiting neuronal degeneration, reducing or inhibiting one or more symptoms associated with neuronal degeneration and/or glaucoma in a subject. The methods include administering a therapeutically effective amount of a isolated mutant erythropoietin EPO polypeptide, an expression vector encoding such a mutant erythropoietin EPO polypeptide, a viral particle including an expression vector, or a composition, thereby treating or inhibiting neuronal degeneration in the subject.

Abstract: Disclosed are isolated mutant erythropoietin (EPO) polypeptides, functional fragment thereof, nucleic acid encoding such peptides, vectors including such nucleic acids and compositions including such peptides and nucleic acids. The mutant EPO peptides are unique in that they include a substitution at amino acid position number 76, such as a glutamic acid for arginine substitution at position 76. This substitution inhibits erythropoietic activity while retaining their neuroprotection. Also disclosed are methods of treating or inhibiting neuronal degeneration, reducing or inhibiting one or more symptoms associated with neuronal degeneration and/or glaucoma in a subject. The methods include administering a therapeutically effective amount of a isolated mutant erythropoietin EPO polypeptide, an expression vector encoding such a mutant erythropoietin EPO polypeptide, a viral particle including an expression vector, or a composition, thereby treating or inhibiting neuronal degeneration in the subject.