Abstract: Examples described herein relate to processor circuitry to issue a cache coherence message to a central processing unit (CPU) cluster by selection of a target cluster and issuance of the request to the target cluster, wherein the target cluster comprises the cluster or the target cluster is directly connected to the cluster. In some examples, the selected target cluster is associated with a minimum number of die boundary traversals. In some examples, the processor circuitry is to read an address range for the cluster to identify the target cluster using a single range check over memory regions including local and remote clusters. In some examples, issuance of the cache coherence message to a cluster is to cause the cache coherence message to traverse one or more die interconnections to reach the target cluster.

Abstract: Nucleotide sequences including a micro-dystrophin gene are provided. The micro-dystrophin genes may be operatively linked to a regulatory cassette. Methods of treating a subject having, or at risk of developing, muscular dystrophy, sarcopenia, heart disease, or cachexia are also provided. The methods may include administering a pharmaceutical composition including the micro-dystrophin gene and a delivery vehicle to a subject. Further, the methods may include administering the pharmaceutical composition a subject having Duchenne muscular dystrophy or Becker muscular dystrophy.

Abstract: The present disclosure relates generally to methods of treating a subject having muscular dystrophy or DMD. The present disclosure also relates generally to methods of prophylactically treating a subject at risk of developing muscular dystrophy or DMD. In some embodiments, the methods may include administering a pharmaceutical composition including an RRM1 gene, an RRM2 gene, and a delivery vehicle to a subject. In another embodiment, the methods may include administering a pharmaceutical composition including an RRM1 gene and an RRM2 gene coupled to a regulatory cassette to a subject. In yet another embodiment, the methods may include administering a pharmaceutical composition including an RRM 1 gene, an RRM2 gene, a regulatory cassette, and a delivery vehicle to a subject.

Abstract: Nucleotide sequences including a micro-dystrophin gene are provided. The micro-dystrophin genes may be operatively linked to a regulatory cassette. Methods of treating a subject having, or at risk of developing, muscular dystrophy, sarcopenia, heart disease, or cachexia are also provided. The methods may include administering a pharmaceutical composition including the micro-dystrophin gene and a delivery vehicle to a subject. Further, the methods may include administering the pharmaceutical composition a subject having Duchenne muscular dystrophy or Becker muscular dystrophy.

Abstract: Nucleotide sequences including a micro-dystrophin gene are provided. The micro-dystrophin genes may be operatively linked to a regulatory cassette. Methods of treating a subject having, or at risk of developing, muscular dystrophy, sarcopenia, heart disease, or cachexia are also provided. The methods may include administering a pharmaceutical composition including the micro-dystrophin gene and a delivery vehicle to a subject. Further, the methods may include administering the pharmaceutical composition a subject having Duchenne muscular dystrophy or Becker muscular dystrophy.

Abstract: Nucleotide sequences including a micro-dystrophin gene are provided. The micro-dystrophin genes may be operatively linked to a regulatory cassette. Methods of treating a subject having, or at risk of developing, muscular dystrophy, sarcopenia, heart disease, or cachexia are also provided. The methods may include administering a pharmaceutical composition including the micro-dystrophin gene and a delivery vehicle to a subject. Further, the methods may include administering the pharmaceutical composition a subject having Duchenne muscular dystrophy or Becker muscular dystrophy.

Abstract: The present invention relates to methods and compositions for the production of viral vectors. In particular, the present invention provides methods and compositions for faster, higher titer and higher purity production of viral vectors (e.g. adenoviral vectors). In some embodiments, the present invention provides gutted and helper viruses with identical or similar termini. In other embodiments, the present invention provides terminal protein linked adenoviral DNA. In certain embodiments, the present invention provides template extended adenoviral DNA.

Abstract: The present invention relates to methods and compositions for the production of viral vectors. In particular, the present invention provides methods and compositions for faster, higher titer and higher purity production of viral vectors (e.g. adenoviral vectors). In some embodiments, the present invention provides gutted and helper viruses with identical or similar termini. In other embodiments, the present invention provides terminal protein linked adenoviral DNA. In certain embodiments, the present invention provides template extended adenoviral DNA.

Abstract: Nucleotide sequences including a micro-dystrophin gene are provided. The micro-dystrophin genes may be operatively linked to a regulatory cassette. Methods of treating a subject having, or at risk of developing, muscular dystrophy, sarcopenia, heart disease, or cachexia are also provided. The methods may include administering a pharmaceutical composition including the micro-dystrophin gene and a delivery vehicle to a subject. Further, the methods may include administering the pharmaceutical composition a subject having Duchenne muscular dystrophy or Becker muscular dystrophy.

Abstract: Compositions and methods for improving cardiac function, myocardial contractility and relaxation in a mammal are provided. Cardiomyocytes transfected with one or more expression vectors comprising a ribonucleotide reductase subunit R1-encoding nucleic acid sequence and a ribonucleotide reductase subunit R2-encoding nucleic acid sequence operably linked to a promoter are grafted to a mammalian myocardium. Also provided are compositions and methods for delivering dATP to a myocardium through grafting of donor cells overexpressing R1 and R2. dATP is thereby produced in situ and delivered through gap junctions established between donor cells and host cardiomyocytes. Alternatively, viral vector(s) having the R1 and R2-encoding construct(s) are administered to the mammal directly. Improvement of cardiac function can also be effected by administration of vectors comprising a nucleic acid sequence encoding a L48Q, 61 Q, or L57Q cTnC variant.

Abstract: Pharmaceutical compositions including a muscle-specific nuclease cassette, one or more guide RNA cassettes, and a delivery system for delivery of the muscle-specific nuclease cassette and the one or more gRNA cassettes are provided. The pharmaceutical composition may also include a mutation-corrected DNA template including a modification to be made in a target nucleic acid sequence. Methods for treating a subject having a muscular or neuromuscular disorder are also provided. The methods may include administering to the subject a therapeutically effective amount of the pharmaceutical composition. Methods of modifying or editing the sequence of a target nucleic acid sequence in a muscle cell are also provided. The methods may include contacting or transducing the muscle cell with a muscle-specific nuclease cassette and one or more gRNA cassettes.

Abstract: The present invention relates to methods and compositions for the production of viral vectors. In particular, the present invention provides methods and compositions for faster, higher titer and higher purity production of viral vectors (e.g. adenoviral vectors). In some embodiments, the present invention provides gutted and helper viruses with identical or similar termini. In other embodiments, the present invention provides terminal protein linked adenoviral DNA. In certain embodiments, the present invention provides template extended adenoviral DNA.

Abstract: The present invention relates to methods and compositions for the production of viral vectors. In particular, the present invention provides methods and compositions for faster, higher titer and higher purity production of viral vectors (e.g. adenoviral vectors). In some embodiments, the present invention provides gutted and helper viruses with identical or similar termini. In other embodiments, the present invention provides terminal protein linked adenoviral DNA. In certain embodiments, the present invention provides template extended adenoviral DNA.

Abstract: Compositions and methods for improving cardiac function, myocardial contractility and relaxation in a mammal are provided. Cardiomyocytes transfected with one or more expression vectors comprising a ribonucleotide reductase subunit R1-encoding nucleic acid sequence and a ribonucleotide reductase subunit R2-encoding nucleic acid sequence operably linked to a promoter are grafted to a mammalian myocardium. Also provided are compositions and methods for delivering dATP to a myocardium through grafting of donor cells overexpressing R1 and R2. dATP is thereby produced in situ and delivered through gap junctions established between donor cells and host cardiomyocytes. Alternatively, viral vector(s) having the R1 and R2-encoding construct(s) are administered to the mammal directly. Improvement of cardiac function can also be effected by administration of vectors comprising a nucleic acid sequence encoding a L48Q, 61 Q, or L57Q cTnC variant.

Abstract: The present invention relates to methods and compositions for the production of viral vectors. In particular, the present invention provides methods and compositions for faster, higher titer and higher purity production of viral vectors (e.g. adenoviral vectors). In some embodiments, the present invention provides gutted and helper viruses with identical or similar termini. In other embodiments, the present invention provides terminal protein linked adenoviral DNA. In certain embodiments, the present invention provides template extended adenoviral DNA.

Abstract: The present invention relates to methods and compositions for the production of viral vectors. In particular, the present invention provides methods and compositions for faster, higher titer and higher purity production of viral vectors (e.g. adenoviral vectors). In some embodiments, the present invention provides gutted and helper viruses with identical or similar termini. In other embodiments, the present invention provides terminal protein linked adenoviral DNA. In certain embodiments, the present invention provides template extended adenoviral DNA.

Abstract: The present invention relates to compositions and methods for expressing mini-dystrophin peptides. In particular, the present invention provides compositions comprising nucleic acid sequences that are shorter than wild-type dystrophin cDNA and that express mini-dystrophin peptides that function in a similar manner as wild-type dystrophin proteins. The present invention also provides compositions comprising mini-dystrophin peptides, and methods for expressing mini-dystrophin peptides in target cells.

Abstract: The present invention relates to nucleic acid compositions and expression systems comprising muscle-specific regulatory elements, and methods for expressing heterologous DNA sequences in cells. In particular, the present invention provides mutant muscle-specific enhancers, genetic cassettes, and vectors useful in gene therapy, diagnostic assays, and other gene expression systems.

Abstract: The present invention relates to methods and compositions for the production of viral vectors. In particular, the present invention provides methods and compositions for faster, higher titer and higher purity production of viral vectors (e.g. adenoviral vectors). In some embodiments, the present invention provides gutted and helper viruses with identical or similar termini. In other embodiments, the present invention provides terminal protein linked adenoviral DNA. In certain embodiments, the present invention provides template extended adenoviral DNA.

Abstract: The present invention relates to methods and compositions for the production of viral vectors. In particular, the present invention provides methods and compositions for faster, higher titer and higher purity production of viral vectors (e.g. adenoviral vectors). In some embodiments, the present invention provides gutted and helper viruses with identical or similar termini. In other embodiments, the present invention provides terminal protein linked adenoviral DNA. In certain embodiments, the present invention provides template extended adenoviral DNA.