Generation of potent dominant negative transcriptional inhibitors
View Patent ↗The present invention provides methods and compositions for regulating gene expression using transcription factors linked to proteins that localize to the transcriptional machinery.
1. A method of inhibiting replication of an immunodeficiency virus, the method comprising the steps of expressing in a cell a nucleic acid construct in an amount sufficient for inhibition of viral transcription, the construct comprising a first nucleic acid sequence encoding HIV-Tat activation domain linked to a second nucleic acid sequence encoding U2AF65, Sfl, 9G8, CstFl, or hnRNP A1.
2. A method of treating a subject infected with an immunodeficiency virus, the method comprising the steps of administering a nucleic acid construct in an amount sufficient for inhibition of viral transcription, the construct comprising a first nucleic acid sequence encoding HIV-Tat activation domain linked to a second nucleic acid sequence encoding U2AF65, Sfl, 9G8, CstFl, or hnRNP A1.
3. The method of claim 1 , wherein the inhibition of transcription is at least 25%.
4. The method of claim 1 , wherein the inhibition of transcription is at least 50%.
5. The method of claim 1 , wherein the inhibition of transcription is at least 75%.
6. The method of claim 1 , wherein the inhibition of transcription is at least 95%.
7. The method of claim 1 , wherein the cell is a T-cell infected with HIV.
8. The method of claim 2 , wherein the inhibition of viral transcription is at least 25%.
9. The method of claim 2 , wherein the inhibition of viral transcription is at least 50%.
10. The method of claim 2 , wherein the inhibition of viral transcription is at least 75%.
11. The method of claim 2 , wherein the inhibition of viral transcription is at least 95%.
12. The method of claim 1 , wherein the second nucleic acid sequence encodes U2AF65.
13. The method of claim 1 , wherein the second nucleic acid sequence encodes Sfl.
14. The method of claim 1 , wherein the second nucleic acid sequence encodes 9G8.
15. The method of claim 1 , wherein the second nucleic acid sequence encodes CstF1.
16. The method of claim 1 , wherein the second nucleic acid sequence encodes hnRNP A 1.
17. The method of claim 2 , wherein the second nucleic acid sequence encodes U2AF65.
18. The method of claim 2 , wherein the second nucleic acid sequence encodes Sfl.
19. The method of claim 2 , wherein the second nucleic acid sequence encodes 9G8.
20. The method of claim 2 , wherein the second nucleic acid sequence encodes CstF1.
21. The method of claim 2 , wherein the second nucleic acid sequence encodes hnRNP A1.