Cell lines for virus production and methods of use
AssigneesUniversity of Georgia Research Foundation, Inc., The United States of America, as represented by the Secretary, Dept. of Health and Human Services, Thermo Fisher Scientific Inc.
InventorsJon Michael Karpilow, Mark Steven Oberste, Ralph A. Tripp, Stephen M. Tompkins
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Abstract
Provided herein are engineered cell lines. In some embodiments, cells of an engineered cell line have altered expression of a gene and/or altered expression of an miRNA, wherein the altered expression results in increased or decreased production of a virus. The virus is a picornavirus, such as a poliovirus or Enterovirus 71. Also provided herein are methods for using the engineered cells to produce virus, and methods for treating a subject having or at risk of having a viral infection.
Claims26
An engineered cell line, wherein cells of the engineered cell line comprise decreased endogenous expression of at least one coding region selected from Table I compared to a control cell line, wherein the at least one coding region is selected from ZNF205, CNTD2, SEC61G, ETS1, TAF1L, MCCD1, LY6G6C, BTN2A1, GLRXL, GCGR, or EP300, and wherein the cells comprise an edited genome that results in decreased endogenous expression of the coding region, wherein the edited genome comprises a mutation of the genomic DNA of the engineered cell compared to a control cell line.
An engineered cell line, wherein cells of the engineered cell line comprise decreased endogenous expression of at least one coding region selected from Table I compared to a control cell line, wherein the at least one coding region is selected from ZNF205, CNTD2, SEC61G, ETS1, TAF1L, MCCD1, LY6G6C, BTN2A1, GLRXL, GCGR, or EP300, wherein the cells comprise a mutation in the coding region or in a regulatory region operably linked to the at least one coding region.
An engineered cell line, wherein cells of the engineered cell line comprise decreased endogenous expression of at least one coding region selected from Table I compared to a control cell line, wherein the at least one coding region is selected from ZNF205, CNTD2, SEC61G, ETS1, TAF1L, MCCD1, LY6G6C, BTN2A1, GLRXL, GCGR, or EP300, wherein the cells further comprise decreased expression of at least one additional coding region selected from Table I, increased expression of an miRNA selected from miR-520e, miR-1256, miR-520d-3p, miR-513a-5p, miR-519c-3p, miR-1270-2, miR-3187, miR-5763p, miR-22, miR-520c-3p, and miR-9 compared to a control cell line, decreased expression of an endogenous miRNA selected from Table IV, or a combination thereof.
An engineered cell, wherein cells of the engineered cell line comprise increased endogenous expression of at least one coding region selected from Table II compared to a control cell line, wherein the cells further comprise increased expression of at least one additional coding region selected from Table II, decreased expression of an endogenous miRNA selected from miR-520e, miR-1256, miR-520d-3p, miR-513a-5p, miR-519c-3p, miR-1270-2, miR-3187, miR-5763p, miR-22, miR-520c-3p, and miR-9 compared to a control cell line, decreased expression of an endogenous miRNA selected from Table IV, or a combination thereof.
An engineered cell line, wherein cells of the engineered cell line comprise decreased endogenous expression of at least one coding region selected from Table I compared to a control cell line, and wherein the at least one coding region is selected from ZNF205, CNTD2, SEC61G, ETS1, TAF1L, MCCD1, LY6G6C, BTN2A1, GLRXL, GCGR, or EP300, and wherein the cells comprise an edited genome that results in decreased endogenous expression of the coding region, and wherein the cells comprise a picornavirus, wherein the edited genome comprises a mutation of the genomic DNA of the engineered cell compared to a control cell line.
An engineered cell line, wherein cells of the engineered cell line comprise increased endogenous expression of at least one coding region selected from Table II compared to a control cell line, wherein the cells comprise a picornavirus, and wherein the picornavirus is an enterovirus 71 or a poliovirus chosen from either Sabin 1, Sabin 2, Sabin 3, Mahoney, Brunhilde, MEF-1, or Saukett.
An engineered cell line, wherein cells of the engineered cell line comprise decreased endogenous expression of at least one coding region selected from Table I compared to a control cell line, wherein the at least one coding region is selected from ZNF205, CNTD2, SEC61G, ETS1, TAF1L, MCCD1, LY6G6C, BTN2A1, GLRXL, GCGR, or EP300, and wherein the cells comprise a picornavirus.
An engineered cell line, wherein cells of the engineered cell line comprise decreased endogenous expression of at least one coding region selected from Table I compared to a control cell line, wherein the cells comprise a mutation in the at least one coding region or in a regulatory region operably linked to the at least one coding region, and wherein the cells comprise a picornavirus.
Dependencies are inferred from the claim text.