My research concentrates in two areas. First, we attempt to improve efficiency of the therapeutic transgene (human factor IX) for gene therapy of hemophilia B, a genetic bleeding disorder. This project involves modification of human factor IX cDNA to yield higher level of factor IX clotting protein, as well as to enhance its specific coagulation activity. Improved factor IX cDNA will enable the use of non-integrating lentiviral vectors in the treatment of hemophilia B.
The second project involves generation and optimization of inducible lentiviral vector-based system in which the expression of the transgene can be switched on and off by using oligonucleotides. The ability to control the period of transgene expression will allow us to avoid or minimize host immune response that acts negatively against transgene products or viral vector-transduced cells.
Suwanmanee T., Hu G(1), Gui T., Bartholomae CC., Kutschera I., von Kalle C., Schmidt M., Monahan PE., and Kafri T. Integration-deficient Lentiviral Vectors Expressing Codon-optimized R338L Human FIX Restore Normal Hemostasis in Hemophilia B Mice. Mol Ther. 2014 Mar;22(3):567-74. doi: 10.1038/mt.2013.188. Epub 2013 Aug 14.
Suwanmanee T*., Svasti S*., Fucharoen S., Moulton HM., Nelson MH., Maeda N., Smithies O., and Kole R. RNA repair restores hemoglobin expression in IVS2-654 thalassemic mice. Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1205-10. Epub 2009 Jan 21. *Suwanmanee T and Svasti S were equally contributed.
Suwanmanee T., Sierakowska H., Fucharoen S. and Kole R. Repair of splicing defect in erythroid cells from patients with beta-thalassemia/HbE disorders. Mol. Ther. 2002 Dec;6(6):718-26.
Suwanmanee T., Sierakowska H., Lacerra G., Svasti S., Kirby S., Walsh CE., Fucharoen S. and Kole R. Restoration of human beta-globin gene expression in murine and human IVS2-654 thalassemic erythroid cells by free uptake of antisense oligonucleotides. Mol. Pharmacol. 2002 Sep;62(3):545-53.