An optimized coding sequence of human blood clotting factor eight (VIII) and a promoter may be used in vectors, such as rAAV, for introduction of factor VIII, and/or other blood clotting factors and transgenes. Exemplary of these factors and transgenes arc alpha-1-antitrypsin, as well as those involved in the coagulation cascade, hepatocye biology, lysosomal storage, urea cycle disorders, and lipid storage diseases. Cells, vectors, proteins, and glycoproteins produced by cells transformed by the vectors and sequence, may be used in treatment.

In one aspect, the embodiments disclosed herein relate to the production of fully-deleted adenovirus-based gen delivery vectors packaged without the use of an adenoviral helper virus, and more particularly in their use in the transfer of genes and the expression of proteins, vaccine development, and cell engineering. In another aspect, the production of adenoviral vectors deleted of all adenoviral genes is described that carry genes of interest with detrimental or toxic activities to eukaryotic cells.

Provided herein are compositions useful for co-administering with a gene therapy vector to a patient having pre-existing neutralizing antibodies to the viral source of the gene therapy vector capsid. The compositions comprise an FcRn ligand which inhibits specific binding between FcRn and IgG.

Provided herein are methods of treating neurodevelopmental disorders, including the treatment of Tuberous sclerosis complex (TSC), with pharmaceutical compositions containing heat shock protein (Hsp) inhibitors and/or mTOR inhibitors. Also provided herein are methods for inhibiting mechanistic target of rapamycin complex 1 (mTORC1) activity and/or increasing or normalizing ciliation.

Methods of inducing an immune response against human immunodeficiency virus (HIV) are described. In particular, methods of inducing an immune response against HIV by co-locally administering an immunogenically effective amount of an isolated HIV envelope (Env) polypeptide and an immunogenically effective amount of an adenovirus vector encoding an HIV antigen, e.g., Env antigen are described. The isolated HIV Env polypeptide and adenovirus vector can be administered in a single composition or in separate compositions, in which the composition or compositions do not contain an adjuvant.

The present invention provides methods and materials useful delivering liquids, including liquids comprising nucleic acid molecules into cells. In particular, the present invention provides methods for delivering saline solution, exogenous compositions, and isolated vectors to kidney cells, using the renal vein as a guide and under hydrodynamic pressure. The delivery methods and materials herein are useful to research, prognose, ameliorate symptoms of kidney injury, and treat kidney pathologies.

The present invention relates to variant AAV capsid polypeptides, wherein the variant AAV capsid polypeptides exhibit increased transduction and/or tropism in human pancreatic tissue or human islets as compared non-variant parent capsid polypeptides.

Non-human animal genomes, non-human animal cells, and non-human animals comprising a humanized TTR locus and methods of using such non-human animal genomes, non-human animal cells, and non-human animals are provided. Non-human animal cells or non-human animals comprising a humanized TTR locus express a human transthyretin protein or a chimeric transthyretin protein, fragments of which are from human transthyretin. Methods are provided for using such non-human animals comprising a humanized TTR locus to assess in vivo efficacy of human-TTR-targeting reagents such as nuclease agents designed to target human TTR. Methods are also provided for making such non-human animals comprising a humanized TTR locus.

Disclosed are nucleic acid vectors comprising a CBh promoter operably linked to a heterologous sequence encoding a G-protein coupled receptor (GPCR). In some embodiments, composition further comprise a sequence encoding an affinity tag, optionally comprising a SNAP polypeptide. In some embodiments, the GPCR comprises a metabotropic glutamate receptor (mGluR), which is optionally, mGluR2. The disclosure also provides compositions and genetically modified cells comprising these vectors. Methods of treatment of retinal diseases and disorders comprising administering compositions, vectors, and cells of the disclosure to a subject in need are also provided.

The present invention relates to a method of amplifying a DNA molecule which is operably-linked to a CARE element in a host cell. The method comprises the step of culturing a host cell which comprises a CARE element operably-linked to the DNA molecule, a nucleotide sequence encoding a L4 22K polypeptide or a variant thereof, a nucleic acid molecule comprising a nucleotide sequence encoding an AAV Rep polypeptide or a variant thereof, and optionally one or more further nucleic acid molecules. The invention also relates to nucleic acid molecules encoding a L4 22K polypeptide or a variant thereof, operably-linked to a heterologous promoter; nucleic acid molecules encoding a CARE element operably-linked to viral genes; processes for producing adenoviral vectors and host cells; and processes for producing viral particles, more preferably AAV particles, in host cells.