Methods of treatment with virus-based gene therapy

Abstract

Methods for treating a patient with virus-based gene therapy that facilitate sustained transgene expression are provided. The methods comprise administering to the patient an inhibitor of an interleukin-6 (IL6) signaling pathway or an NCOR2 / SMRT histone deacetylation pathway, and a virus-based gene therapy vector. Also provided are methods for assigning a virus-based gene therapy to a patient, the method comprises by evaluating whether the patient has a mutation associated with reduced SMRT / NCOR2 protein function in the SMRT / NCOR2 gene or interleukin-6 receptor (IL-6R) Mutations in the gene associated with reduced IL-6R function determine whether the patient has a genotype that sensitizes the patient to persistent infections achieved by virus-based gene therapy vectors. If the patient has a mutation in the SMRT / NCOR2 gene associated with a reduced SMRT / NCOR2 protein function or a mutation in the IL-6R gene associated with a reduced IL-6R function, a virus-based gene therapy vector is assigned to the patient.

Description

[0001] Cross References to Related Applications [0002] This application claims priority to U.S. Provisional Patent Application No. 62 / 864,404, filed June 20, 2019, and U.S. Provisional Patent Application No. 62 / 867,172, filed June 26, 2019, the contents of which are They are hereby incorporated by reference in their entirety for all purposes. [0003] funding statement [0004] This invention was made in part with government support under Grant No. NIH NHLBI RC3 HL103396-01 awarded by the National Institutes of Health. The government may have certain rights in this invention. Background technique [0005] Several clinical studies have demonstrated the use of DNA viral vectors derived from non-pathogenic adeno-associated virus (AAV) for the successful delivery of transgenes to patients in need of gene therapy, such as those with hemophilia B. AAV vector constructs are generated by replacing the viral gene with a therapeutic cassette consisting of a promoter, a transgene of...

AI Technical Summary

Problems solved by technology

This has several disadvantages, including the cost and inconvenience of frequent prophylactic infusions (up to 3 times per week), the need to plan physical activity around peaks and troughs in clotting factor levels, and the potential for breakthrough bleeding

Despite management with alternative therapies, hemophilia B still has a considerable negative impact on the daily lives of affected individuals

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