G2B: an optimized lentiviral vector with enhanced titer and β-globin expression for improved β-thalassemia gene therapy
Year: 2025
Type: article
Abstract: Gene therapy using lentiviral vectors offers a promising alternative treatment for β-thalassemia, a common monogenic blood disorder. Although the BB305 vector has demonstrated long-term clinical success—enabling most β-thalassemia patients to become transfusion-independent and substantially reducing vaso-occlusive events in sickle cell disease—there remains a significant opportunity to enhance its efficacy and lower production costs. Here, we present G2B, a novel hemoglobin beta gene (HBB) lentiviral vector derived from BB305-like constructs (BB305L), engineered by shortening the locus control region (LCR) and incorporating a mutated HBG2 promoter. Compared to BB305L, G2B achieves a ~4-fold increase in lentiviral titer and a 60% boost in β-globin expression. In a transplantation model using Hbbth4/Hbb+ hematopoietic stem/progenitor cells, G2B demonstrates robust therapeutic efficacy without compromising integration safety. These findings suggest that G2B may offer a more potent, efficient, and potentially cost-effective gene therapy option for β-thalassemia and other hemoglobinopathies.
Source: Blood Science
Authors: Zhu-Ying Gao, Zhi-Xue Yang, Dong-Hao Deng, Feng Zhang, Bing Yu, Yang-Yang Zhang, Xiang Lv, Yukio Nakamura, An Gong, Tao Cheng, Jian-Ping Zhang, Xiao-Bing Zhang
Institutions: Chinese Academy of Medical Sciences & Peking Union Medical College, Institute of Hematology & Blood Diseases Hospital, State Key Laboratory of Experimental Hematology, China University of Petroleum, East China, Institute of Basic Medical Sciences of the Chinese Academy of Medical Sciences, State Key Laboratory of Medical Molecular Biology, RIKEN BioResource Research Center
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W4415202074