Abstract: Compositions and methods are described for the delivery of a fully human post-translationally modified therapeutic monoclonal antibody that binds to CGRP or CGRP receptor to a human subject for the treatment or prevention of migraines and cluster headaches. The antibodies may be delivered by gene therapy vectors, particularly rAAV vectors. Also provided are dual transgene constructs for the delivery of anti-CGRP and anti-CGRP receptor antibodies or antigen binding fragments thereof.

Abstract: The present invention relates to recombinant adeno-associated viruses (rAAVs) having capsid proteins engineered to include amino acid sequences and/or amino acid substitutions that confer and/or enhance desired properties, particularly increased transduction in CNS or muscle cells relative to a rAAV having a reference capsid.

Abstract: The present invention provides mutant adeno-associated virus serotype 5 (AAV5) that exhibit altered capsid properties, e. g., increased infectivity in human liver cells and/or minimal binding to human neutralizing antibodies. The present invention further provides libraries of mutant AAV5 comprising one or more mutations in a capsid gene. The present invention further provides methods of generating the mutant AAV5 and mutant AAV5 libraries, and compositions comprising the mutant AAV5. The present invention further provides recombinant AAV5 (rAAV5) virions that comprise a mutant capsid protein. The present invention further provides nucleic acids comprising nucleotide sequences that encode mutant capsid proteins.