Lentivirus (lente-, Latin for “slow”) is a genus of retroviruses, causing chronic and deadly diseases by long incubation periods in human or other mammalian species [1]. The virion is a medium-sized (80-100nm) and enveloped, slightly pleomorphic, spherical with an isometric nucleocapsid containing two copies of positive-sense ssRNA genome. Most lentiviral vectors are based on the Human Immunodeficiency Virus (HIV), which causes AIDS. To date, 5 serogroups have been recognized according to the vertebrate hosts they are associated with (primates, sheep and goats, horses, domestic cats, and cattle). Among them, the primate lentiviruses are distinguished by the utilization of CD4 surface protein as a receptor and the absence of dUTPase [2]. Considering the key safety concerns during the use of HIV-derived lentivirus vectors, recombinant lentivirus has been designed and widely used for gene delivery in most cell types.
Derived from HIV-1, lentiviruses can integrate a significant amount of viral cDNA into the host genome, mediate stable and long-term transgene expression, and efficiently infect dividing cells and nondividing cells, which makes lentivirus an attractive gene delivery vehicles in most cell types [3].
Indication | Transplants | Delivery route | Phase | Sponsor |
β-Thalassemia | Autologous CD34+ cells transduced with Lenti-TNS9.3.55 | Intravenous | I | Memorial Sloan Kettering Cancer Center |
Autologous CD34+ cells transduced with LentiGlobin BB305 | Intravenous | Ⅲ | bluebird bio | |
Autologous CD34+ cells transduced with LentiGlobin BB305 | Intravenous | I–II | bluebird bio | |
Autologous CD34+ cells transduced with Lenti- β-globin | Intravenous | I–II | IRCCS San Raffaele | |
X-linked adrenoleukodystrophy | Lenti-ABCD1 | Intracerebral | I–II | Shenzhen Geno-Immune Medical Institute |
Autologous CD34+ cells transduced with Lenti-ABCD1 | Intravenous | I–II | Shenzhen Second People’s Hospital | |
Wiskott-Aldrich Syndrome | Autologous CD34+ cells transduced with Lenti-WAS gene | Intravenous | I–II | Genethon |
Autologous CD34+ cells transduced with Lenti-WAS gene | Intravenous | II | GlaxoSmithKline | |
Autologous CD34+ cells transduced with Lenti-WAS gene | Intravenous | I–II | Genethon | |
Autologous CD34+ cells transduced with Lenti-WAS gene | Intravenous | I–II | Genethon | |
Metachromatic leukodystrophy | Lenti-ARSA | intracerebral | Not applicable | Not applicable |
Autologous CD34+ stem cells transduced with Lenti-ARSA | Intravenous | II | GlaxoSmithKline | |
Autologous CD34+ stem cells transduced with Lenti-ARSA | Intravenous | I–II | Shenzhen Second People’s Hospital | |
Sickle cell disease | Lenti-gamma-globin | Intravenous | I–II | Children’s Hospital Medical Center, Cincinnati |
Autologous CD34+ stem cells transduced with Lenti-βAS3-FB | Intravenous | I | Donald B. Kohn, M.D. | |
Autologous CD34+ cells transduced with LentiGlobin BB305 | Intravenous | I | Bluebird bio | |
Autologous CD34+ cells transduced with Lenti-shBCL11a | Intravenous | I | David Williams | |
Fanconi anemia | Autologous CD34+ cells transduced with Lenti- FANCA | Intravenous | I | Fred Hutchinson Cancer Research Center |