Abstract:
Provided are methods of treating a subject in need of treatment for a disease caused by a loss of function or activity of a protein. Also provided are methods of treating a subject in need of treatment for a disease caused by a gain of function, activity or expression, of a protein.
Abstract:
Methods and uses of treating a disease in a mammal are provided by administering to a mammalian non-central nervous system (CNS) cell, organ or tissue, for delivery to mammalian CNS (e.g., brain). Methods and uses of treating a disease in a mammal include, inter alia, administering to a mammalian non-ocular cell, organ or tissue for delivery to a mammalian ocular cell, organ or tissue.
Abstract:
Cells and cell lines are disclosed that are able to produce therapeutic proteins, antibodies, vectors, and viral vectors such as lentiviral vectors and adeno-associated viral (AAV) vectors. The cells and/or cell lines can have mutations or deletions in either one or both of the endogenous di-hydrofolate reductase (DHFR−/−) or glutamine synthetase (GS−/−) genes such that DHFR and/or GS expression or function is substantially reduced or eliminated.
Abstract:
CpG reduced nucleic acid variants encoding FVIII protein and methods of use thereof are disclosed. In particular embodiments, CpG reduced nucleic acid variants encoding FVIII are expressed more efficiently by cells, are secreted at increased levels by cells over wild-type Factor VIII proteins, exhibit enhanced expression and/or activity over wild-type Factor VIII proteins or are packaged more efficiently into viral vectors.
Abstract:
CpG reduced nucleic acid variants encoding FVIII protein and methods of use thereof are disclosed. In particular embodiments, CpG reduced nucleic acid variants encoding FVIII are expressed more efficiently by cells, are secreted at increased levels by cells over wild-type Factor VIII proteins, exhibit enhanced expression and/or activity over wild-type Factor VIII proteins or are packaged more efficiently into viral vectors.
Abstract:
The presently disclosed subject matter relates to compositions and methods for regulating recombinant adeno-associated virus (rAAV) production in cell culture. In particular, the presently disclosed subject matter relates to strategies to overcome AAV Rep protein-mediated cytotoxicity by reversible post-translational regulation of the expression of AAV Rep and helper proteins, resulting in regulated rAAV production.
Abstract:
The invention provides expression cassettes. In certain embodiments, an expression cassette comprises (a) a regulatory element at least 90% identical to the sequence of any of SEQ ID NOs:2-67, and (b) a nucleic acid sequence encoding a Factor VIII protein having a B domain deletion (FVIII-BDD), where the nucleic acid sequence of (a) is at least 90% identical to the sequence of SEQ ID NO:77, where the regulatory element is operably linked to the nucleic acid sequence, and where no intron is present between the regulatory element and the nucleic acid sequence encoding FVIII-BDD, or where no more than 0-107 nucleotides of untranslated nucleic acid is between the regulatory element and the nucleic acid sequence encoding FVIII-BDD. In certain embodiments, expression cassettes contain sequence elements having CpG(s) substituted with CpT, CpA, TpG, or ApG at the same position(s) or has CpG reduced nucleic acid sequences.
Abstract:
Disclosed herein are methods for analyzing for or detecting the presence of non-antibody inhibitors and/or enhancers of adeno-associated virus (AAV) vector cell transduction in a biological sample from a subject. Also disclosed herein are methods for analyzing for, or detecting the presence of, AAV binding antibodies that inhibit, reduce or decrease AAV vector cell transduction in a biological sample from a subject. The methods rely, in part, on the use of empty capsid AAV particles to absorb AAV binding antibodies, to detect enhancers or inhibitors of AAV vector cell transduction, when present, in a biological sample analyzed for AAV neutralizing antibodies (NAbs).
Abstract:
The invention provides nucleic acids encoding acid a-glucosidase (GAA). In certain embodiments, nucleic acids have greater than about 86% sequence identity to a sequence selected from the group consisting of any of the sequences set forth as SEQ ID NOs:1-5. In certain embodiments, nucleic acids encoding acid a-glucosidase (GAA) contain less than 127 CpG dinucleotides. Expression cassettes, vectors, cells and cell lines and methods of using such nucleic acids encoding acid a-glucosidase (GAA) are also provided.
Abstract:
Disclosed herein are compositions and methods of treating and/or correcting ocular disease in a subject, such as a mammal (e.g., human) eye using an Adeno-associated virus (AAV) system. The AAV system employs a nucleic acid encoding a CRISPR-Cas9 system for targeted gene disruption or correction.