High-transducing HSV vectors
Disclosed herein are high transducing replication defective herpes simplex virus (HSV) vectors of McKrae strain.
1. A gene therapy vector comprising a replication-defective variant of herpes simplex virus (HSV) McKrae strain whose genome contains an alteration such that the variant fails to express a functional ICP4 protein comprising SEQ ID NO: 16, wherein the gene therapy vector is capable of expressing a payload in neurons for at least 18 days.
2. The gene therapy vector of claim 1 , wherein the gene therapy vector comprises a neuron specific promoter.
3. The gene therapy vector of claim 2 , wherein the neuron specific promoter is a calcitonin gene-related peptide (CGRP) promoter.
4. The gene therapy vector of claim 1 , wherein the gene therapy vector comprises a human cytomegalovirus (HCMV) enhancer.
5. The gene therapy vector of claim 1 , wherein the gene therapy vector comprises a bovine growth hormone (BGH) polyadenylation signal.
6. The gene therapy vector of claim 1 , further comprising a nucleic acid that encodes a therapeutic polypeptide.
7. A cell transduced with a gene therapy vector according to claim 1 .
8. A pharmaceutical composition comprising a gene therapy vector according to claim 1 and a pharmaceutically acceptable carrier.
9. The gene therapy vector of claim 1 , wherein the functional ICP4 protein has an amino acid sequence of SEQ ID NO: 2.
10. The gene therapy vector of claim 1 , wherein the gene therapy vector is capable of expressing a payload in neurons for at least 50 days.
11. The gene therapy vector of claim 1 , wherein the gene therapy vector is capable of expressing a payload in neurons for at least 100 days.
12. The gene therapy vector of claim 1 , wherein the gene therapy vector is capable of producing in neurons a mean genome copy number of greater than 5,000 transcripts.
13. The gene therapy vector of claim 1 , wherein the gene therapy vector is capable of producing in neurons a mean genome copy number of greater than 10,000 transcripts.
14. The gene therapy vector of claim 1 , wherein the gene therapy vector is capable of producing in neurons a mean genome copy number of greater than 15,000 transcripts.