Abstract: Genome editing systems, guide RNAs, and CRISPR-mediated methods are provided for altering portions of the HBG1 and HBG2 loci, portions of the erythroid specific enhancer of the BCL11A gene, or a combination thereof, in cells and increasing expression of fetal hemoglobin.

Abstract: Provided herein are CRISPR/Cas-related methods and components for editing a target nucleic acid sequence in a HBG1 and/or HBG2 gene regulatory region, and applications thereof in connection with methods of increasing expression of fetal hemoglobin and treating ?-hemoglobinopathies including sickle cell disease and ?-thalassemia.

Abstract: A heat conducting insert for a reactor includes an elongated center portion, a cross member extending outwardly from the center portion and an outer portion extending laterally from a distal end of the cross member. A reactor includes a shell and an insert in the shell. The insert includes an elongated center portion, a cross member extending outwardly from the center portion, and an outer portion extending laterally from a distal end of the cross member.

Abstract: The invention features compositions and methods for introducing mutations into the hepatitis B virus (HBV) genome.

Abstract: Provided herein are improved prime editing methods and compositions that allow for efficient and precise editing of target genes.

Abstract: The present invention provides novel systems, methods and compositions for making and using recombinantly engineered novel Cas9 enzymes optimized for human cells, for nucleic acid targeting and manipulation. The present invention is based on the discovery of novel Cas9 enzymes from Streptococcus constellatus, Sharpen spp. isolate RUG017, Veillonella parvula, Ezakiella peruensis, Lactobacillus fermentum strain AF15-40LB strain and Peptoniphilus sp. Marseille-P3761 bacteria that were codon-optimized and recombinantly produced for use in human cells. In some embodiments, novel Cas9 enzymes can be used for base editing. In some embodiments, the novel engineered Cas9 enzymes are used to treat human diseases.

Abstract: Genome editing systems, guide RNAs, dead guide RNAs, and CRISPR-mediated methods are provided for altering portions of a target nucleic acid.

Abstract: Genome editing systems, guide RNAs, and CRISPR-mediated methods are provided for altering portions of the HBG1 and HBG2 loci, portions of the erythroid specific enhancer of the BCL11A gene, or a combination thereof, in cells and increasing expression of fetal hemoglobin.

Abstract: Disclosed are methods and compositions for determining immunodominant peptides of target enzymes used in enzyme replacement therapy for lysosomal storage disorders. More specifically disclosed are immunodominant peptides for N-acetylgalactosamine-6-sulfatase (GALNS). Also disclosed are methods of inducing oral tolerance towards a target enzyme through oral administration of immunodominant peptides prior to commencing enzyme replacement therapy. More specifically disclosed is a method of inducing oral tolerance for GALNS, by orally administering specific immunodominant peptides for GALNS; in subjects suffering from mucopolysaccharidosis type IVA prior to commencing enzyme replacement therapy using GALNS.

Abstract: The present disclosure is directed to methods of producing a modified nucleic acid comprising a precise deletion in a target nucleic acid in a cell comprising generating, within the cell, a first single strand break on a first strand of the target nucleic acid and a second single strand break on a second strand of the target nucleic acid, thereby forming a double strand break in the target nucleic acid having a first 3? overhang and a second 3? overhang; processing the first 3? overhang and the second 3? overhang with an exonuclease molecule, thereby deleting the segment of the target nucleic acid that was located between the first single strand break and the second single strand break, and forming a processed double strand break; and allowing the processed double strand break to be repaired by at least one DNA repair pathway, thereby producing the modified nucleic acid comprising the precise deletion in the target nucleic acid in the cell.

Abstract: The present invention provides novel systems, methods and compositions for making and using a recombinantly engineered novel Cas9 optimized for human cells, for nucleic acid targeting and manipulation. The present invention is based on the discovery of a novel Cas9 species from Lachnospira bacterium that was codon-optimized and recombinantly produced for use in human ceils. In some embodiments, the novel Cas9 can be used in a base editor. In some embodiments, the novel engineered Cas9 is used to treat human diseases.

Abstract: The present disclosure is directed to methods of producing a modified nucleic acid comprising a precise deletion in a target nucleic acid in a cell comprising generating, within the cell, a first single strand break on a first strand of the target nucleic acid and a second single strand break on a second strand of the target nucleic acid, thereby forming a double strand break in the target nucleic acid having a first 3? overhang and a second 3? overhang; processing the first 3? overhang and the second 3? overhang with an exonuclease molecule, thereby deleting the segment of the target nucleic acid that was located between the first single strand break and the second single strand break, and forming a processed double strand break; and allowing the processed double strand break to be repaired by at least one DNA repair pathway, thereby producing the modified nucleic acid comprising the precise deletion in the target nucleic acid in the cell.

Abstract: The invention features compositions and methods for introducing mutations into the hepatitis B virus (HBV) genome.

Abstract: Disclosed are methods and compositions for determining immunodominant peptides of target enzymes used in enzyme replacement therapy for lysosomal storage disorders. More specifically disclosed are immunodominant peptides for N-acetylgalactosamine-6-sulfatase (GALNS). Also disclosed are methods of inducing oral tolerance towards a target enzyme through oral administration of immunodominant peptides prior to commencing enzyme replacement therapy. More specifically disclosed is a method of inducing oral tolerance for GALNS, by orally administering specific immunodominant peptides for GALNS; in subjects suffering from mucopolysaccharidosis type IVA prior to commencing enzyme replacement therapy using GALNS.

Abstract: The present disclosure relates to methods of assessing a sample of guide RNAs (gRNAs).

Abstract: The present invention features compositions and methods for editing a gene associated with Shwachman Diamond Syndrome (SDS) using a programmable nucleobase editor, such that the gene is permissive for transcription and generates a functional gene product (e.g., providing a splice site and/or altering a nonsense mutation).

Abstract: Disclosed are methods and compositions for determining immunodominant peptides of target enzymes used in enzyme replacement therapy for lysosomal storage disorders. More specifically disclosed are immunodominant peptides for N-acetylgalactosamine-6-sulfatase (GALNS). Also disclosed are methods of inducing oral tolerance towards a target enzyme through oral administration of immunodominant peptides prior to commencing enzyme replacement therapy. More specifically disclosed is a method of inducing oral tolerance for GALNS, by orally administering specific immunodominant peptides for GALNS; in subjects suffering from mucopolysaccharidosis type IVA prior to commencing enzyme replacement therapy using GALNS.

Abstract: CRISPR/CAS-related compositions and methods for treatment of beta hemoglobinopathies are disclosed.

Abstract: The present disclosure relates to methods of assessing a sample of guide RNAs (gRNAs).

Abstract: Genome editing systems, guide RNAs, and CRISPR-mediated methods are provided for altering portions of the HBG1 and HBG2 loci, portions of the erythroid specific enhancer of the BCL11A gene, or a combination thereof, in cells and increasing expression of fetal hemoglobin.