The present invention relates to the field of the production of lentiviral vectors (LV) for gene therapy. More particularly, the invention relates to a system to obtain the stable integration of a Self Inactivating (SIN) lentiviral transfer vector into a packaging cell line. The SIN lentiviral transfer vector is integrated using a DNA fragment containing the Inverted Terminal Repeats (ITR) of Adeno Associated Virus (AAV), thus obtaining the stable producer cell line for SIN lentiviral vectors.

The disclosure features compositions and methods for the treatment of sensorineural hearing loss and auditory neuropathy, particularly forms of the disease that are associated with mutations in otoferlin (OTOF), by way of OTOF gene therapy. The disclosure provides a variety of compositions that include a first nucleic acid vector that contains a polynucleotide encoding an N-terminal portion of an OTOF protein and a second nucleic acid vector that contains a polynucleotide encoding a C-terminal portion of an OTOF protein. These vectors can be used to increase the expression of OTOF in a subject, such as a human subject suffering from sensorineural hearing loss.

A gene therapy treatment for alpha 1-antitrypsin (AAT) deficiency is provided comprising a plasmid or viral, e.g., an AAV, vector coding for an elastase- or cathepsin G-inhibiting, oxidation-resistant human AAT with a substitution at, for example, Met358 and/or Met351.

Described herein are methods and compositions for treating MPSII (Hunter) disease.

Provided herein are compositions that include at least two different nucleic acid vectors, where each of the at least two different vectors includes a coding sequence that encodes a different portion of an otoferlin protein, and the use of these compositions to treat hearing loss in a subject.

The disclosure features compositions and methods for the treatment of sensorineural hearing loss and auditory neuropathy, particularly forms of the disease that are associated with mutations in otoferlin (OTOF), by way of OTOF gene therapy. The disclosure provides a variety of compositions that include a first nucleic acid vector that contains a polynucleotide encoding an N-terminal portion of an OTOF protein and a second nucleic acid vector that contains a polynucleotide encoding a C-terminal portion of an OTOF protein. These vectors can be used to increase the expression of OTOF in a subject, such as a human subject suffering from sensorineural hearing loss.

The present invention provides methods, compositions, and kits for preparing and using adeno associated virus and baculovirus. The methods for producing adeno associated virus and baculovirus particles include using histidine rich peptides and other cationic peptides as transfection reagents. The adeno associated virus are pseudotyped with capsids, in particular for use in gene therapy and/or diagnostics. The baculovirus are also used to prepare adeno associated virus.

This invention relates generally to compositions for making and administering anellovectors and uses thereof.

The invention described herein provides a recombinant replication-defective virus derived from Herpesvirales order, comprising a defective ICP27 gene that impairs or otherwise does not support replication of the HSV, or a functional equivalent gene thereof; a gene-of-interest (GOI) flanked by AAV ITR sequences inserted at, within, or replacing a non-essential or replaceable essential locus of the HSV; and a coding sequence for AAV Rep and Cap proteins inserted at, within or replacing the non-essential or replaceable essential locus of the HSV. The invention also provides production cell lines for such recombinant replication-defective virus, wherein the cell lines have a coding sequence for ICP27 or a functional equivalent thereof, and wherein the coding sequence has no or minimal sequence overlap with the virus characterized by the defective ICP27 gene that impairs or otherwise does not support replication of the HSV. Methods of using such recombinant replication-defective virus and production cell lines are also provided. rAAV produced using such recombinant replication-defective virus and/or production cell lines and methods of making such rAAV are also provided.

The disclosure features compositions and methods for the treatment of sensorineural hearing loss and auditory neuropathy, particularly forms of the disease that are associated with mutations in otoferlin (OTOF), by way of OTOF gene therapy. The disclosure provides a variety of compositions that include a first nucleic acid vector that contains a polynucleotide encoding an N-terminal portion of an OTOF protein and a second nucleic acid vector that contains a polynucleotide encoding a C-terminal portion of an OTOF protein. These vectors can be used to increase the expression of OTOF in a subject, such as a human subject suffering from sensorineural hearing loss.