Lentiviral Vectors for Gene Therapy

Abstract

Lentiviral vector (LV) originated from human immunodeficiency virus is the common gene transfer vector in gene therapy. With the development over the past two decades, the safety, specific targeting and transduction efficiency of LV have been improved continually. In terms of safety, the virus genome was split into several plasmids and their accessory gene elements were removed. Specific viral envelope protein and posttranscriptional regulatory elements were introduced in LV system for the tissues' specific targeting and transduction efficiency. Based on these improvements, LV has been used widely in gene therapy especially for treatments of haemoglobinopathies, B cell leukaemia, immunodeficiency diseases and neurodegenerative diseases. Key Concepts Lentiviral vector derived from the human immunodeficiency virus and its development needs the evaluation and selection of virus genome elements for safe and efficient gene transfer. Lentiviral vector has shown its efficiency and safety in many clinical trials and approved gene therapy drugs. For the transduction efficiency, specific target and safety, lentiviral vector is modified and improved continuously. Currently, scientists focus on the more effective promoter, specific envelope protein, and inducible and regulatable expression system. The random insertional mutagenesis and high production cost remain the challenges in the lentiviral vector application. Lentiviral vector performs well in haematological and immune system partial due to the ex vivo transduction and transfusion back into blood flow which circumvent the shortage like relative lower titre and insertional mutagenesis.

Duchenne muscular dystrophy treatment with lentiviral vector containing mini‐dystrophin gene in vivo

“…In contrast, the characteristics of LVs, such as large packaging capacity and low immunogenicity, raised our interest. 40 Therefore, we administered LVs carrying a modified human dystrophin sequence to mdx mice. We found that the LVs were able to transmit the genetic material into muscle tissues, express the sequences, and alleviate the disease progression.…”

“…However, the packaging ability and immunogenicity of AAV still restricted their clinical application. In contrast, the characteristics of LVs, such as large packaging capacity and low immunogenicity, raised our interest 40 . Therefore, we administered LVs carrying a modified human dystrophin sequence to mdx mice.…”

Split‐Cas9‐based targeted gene editing and nanobody‐mediated proteolysis‐targeting chimeras optogenetically coordinated regulation of Survivin to control the fate of cancer cells

“…Lentiviruses have a wide range of hosts, a large gene capacity, high infection efficiency and long‐term stable expression by integrating genes into host cells 37 . Recently, it has been widely used in studying genetic mechanisms and disease development 35–37 . Hence, lentiviral vectors can be chosen to deliver the paCas9 and paProtacL systems to reduce Survivin expression in cancers effectively.…”

“…All the above studies showed that inhibiting the expression of Survivin could be used to treat cancers and reduce the generation of chemoresistance. Meanwhile, the choice of an efficient delivery system is necessary for better gene delivery 35,36 . Lentiviruses have a wide range of hosts, a large gene capacity, high infection efficiency and long‐term stable expression by integrating genes into host cells 37 .…”

“…Meanwhile, the choice of an efficient delivery system is necessary for better gene delivery. 35 , 36 Lentiviruses have a wide range of hosts, a large gene capacity, high infection efficiency and long‐term stable expression by integrating genes into host cells. 37 Recently, it has been widely used in studying genetic mechanisms and disease development.…”