TNS9

TNS9 is a lentiviral vector based on HIV-1 that encodes the human β-globin gene. It was developed for **gene therapy applications**, particularly for the treatment of β-thalassemia major. The vector design is sophisticated, including the β-globin promoter, two proximal enhancers, and three large segments encompassing HS2, HS3, and HS4 [5]. A critical modification in TNS9 was the deletion of a cryptic polyadenylation site within intron 2 of the β-globin gene to improve expression [5]. The vector is used in a process involving autologous hematopoietic stem cell transplantation: stem cells are collected from patients with β-thalassemia major, transduced *ex vivo* with the TNS9 vector to introduce the corrected gene, and then returned to the patient via intravenous injection [4]. This requires patients to receive low-dose busulfan conditioning to prepare the bone marrow [4]. TNS9 has evolved through iterations, with the current clinical version appearing to be TNS9.3.55, which includes insulator elements and is used at Memorial Sloan Kettering Cancer Center [8]. This vector is part of a product called Thalagen, developed by San Rocco Therapeutics [6]. Laboratory testing of TNS9.3 showed high transduction efficiency (average 97.2% in human CD34+ cells at MOI 50) and successful human β-globin expression *in vitro* [5]. Clinical trials began around 2012-2013, with initial reports of safe and effective treatment in patients with Beta-Thalassemia Major [4]. The development represents a significant advance for inherited blood disorders, potentially offering a curative option.

Brand names

Thalagen