The disclosed invention relates to safe and efficacious methods of extending postvaccinal immunity against severe acute respiratory syndrome virus SARS-CoV-2 and revaccinating a population against diseases caused by SARS-CoV-2. The disclosed methods include administration of an agent to a person or population. The agent may include a first component comprising an expression vector based on a genome of recombinant strain of (i) human adenovirus serotype 26 with the E1 and E3 sites deleted from the genome and the site ORF6-Ad26 substituted for ORF6-Ad5 with an integrated expression cassette selected from SEQ ID NO:1, SEQ ID NO:2, or SEQ ID NO:3, or (ii) a simian adenovirus serotype 25 with the E1 and E3 sites deleted from the genome with an integrated expression cassette selected from SEQ ID NO:4, SEQ ID NO:2, or SEQ ID NO:3. The first component of the agent is combined or replaced with a second component in the form of an expression vector based on a genome of recombinant strain of human adenovirus serotype 5 with the E1 and E3 sites deleted from the genome with an integrated expression cassette selected from SEQ ID NO:1, SEQ ID NO:2, or SEQ ID NO:3. In addition to the above, the method may include administering an agent as disclosed herein, wherein the first component or the second component has the form of an expression vector based on genome of recombinant strain of human adenovirus serotype 5 with E1 and E3 sites deleted from the genome with the integrated expression cassette selected from SEQ ID NO:1, SEQ ID NO:2, or SEQ ID NO:3.

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 application provides gene therapies for treating monogenic forms of nephrotic syndrome.

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 disclosure provides a conjugate comprising an affinity agent, a branched linker, and two or more photoisomerizable regulators. The present disclosure provides compositions comprising the conjugate, as well as devices comprising the compositions. The present disclosure provides methods for enhancing visual function, the methods comprising administering the conjugate to an individual in need thereof.

The present invention describes the development of a modified envelope glycoproteins to pseudo-type viruses of the retroviridae family. These are derived from Murine leukaemia virus amphotropic, Gibbon Ape leukaemia virus and feline endogenous virus envelopes.

The improved envelope glycoproteins contain, among other modifications, newly introduced alternative cleavable sequences.

The viral vectors pseudo-typed with these modified envelopes may be suitably employed for cargo delivery such as in gene and cell therapy applications, for the ex vivo and in vivo delivery of gene(s), protein(s), or molecule(s) of interest to a variety of target cells.

A nucleic acid trans-splicing molecule is provided that can replace an exon in a targeted mammalian ocular gene carrying a defect or mutation causing an ocular disease with an exon having the naturally-occurring sequence without the defect or mutation. The trans-splicing molecule includes a 3′ transcription terminator domain which enhances the efficiency of trans-splicing. The 3′ TTD comprises a triple helix domain and a tRNA-like domain.

The present invention relates to a Crumbs homologue (CRB) therapeutic for use as a medicament or in a method of treatment or prophylaxis, for example in the treatment or prophylaxis of a retinal disorder due to mutations in the Crumbs homologue-1 (CRB1) gene, such as Leber's congenital amaurosis 8 (LCA8) or retinitis pigmentosa 12 (RP12). In particular, the present invention relates to a recombinant viral vector comprising CRB2 or modified non-toxic forms of either CRB1 or CRB3 that resemble CRB2.

Provided are therapeutic virus vectors, particularly, recombinant adeno-associated virus (rAAV) vectors, designed to contain an enhancer sequence that specifically restricts expression of an effector gene (e.g., an SCN1A-encoding polynucleotide, Gq-DREADD-encoding polynucleotide, or PSAM-encoding polynucleotide) contained in the vector to PV-expressing GABAergic interneuron or to neuron cell populations in the brain. The rAAV vectors, compositions and methods thereof are useful for treating subjects afflicted with neuropathologies, seizures, pharmacologically-intractable forms of epilepsy including Dravet syndrome (DS), a form of infantile epilepsy associated with severe seizures, cognitive impairment and premature death, as the cause of DS involves loss of function of a sodium channel encoded by the SCN1A gene. The described vectors restore expression of effector genes to the appropriate interneuron or neuron cell populations with specificity and sensitivity, advantageously to address the root cause of the disease by restoring the excitation-inhibition balance by means of gene-therapy (with SCN1A) or pharmacogenetics.

Provided herein are methods and constructs related to minimizing immune responses using modified dexamethasone compounds when administering a desired transgene in a cell achieved by delivery of the transgene with one or more doses of a ceDNA construct.