Lentiviral

Lentiviral Vectors

Lentiviral vectors are a type of viral vector derived from lentiviruses, which are a subclass of retroviruses. These vectors are widely used in molecular biology and gene therapy due to their ability to integrate into the host cell genome and transduce non-dividing cells. This article provides a comprehensive overview of lentiviral vectors, their structure, applications, and safety considerations.

Structure and Function

Lentiviruses are enveloped viruses with a single-stranded RNA genome. The most well-known lentivirus is the Human Immunodeficiency Virus (HIV), which has been extensively studied and modified to create safe and effective lentiviral vectors. The key components of a lentiviral vector include:

• Envelope Protein: Typically derived from the vesicular stomatitis virus (VSV-G), this protein facilitates the entry of the vector into a wide range of host cells.
• Gag-Pol Polyprotein: Encodes structural proteins and enzymes necessary for viral replication, such as reverse transcriptase and integrase.
• Transfer Vector: Contains the transgene of interest flanked by long terminal repeats (LTRs) and necessary regulatory elements.

Applications

Lentiviral vectors are used in various applications, including:

• Gene Therapy: Due to their ability to stably integrate into the host genome, lentiviral vectors are used to deliver therapeutic genes to treat genetic disorders such as Severe Combined Immunodeficiency (SCID) and Beta-thalassemia.
• Basic Research: Researchers use lentiviral vectors to study gene function and regulation by delivering shRNA or CRISPR/Cas9 components to knockdown or edit genes in vitro and in vivo.
• Vaccine Development: Lentiviral vectors are being explored as platforms for vaccine delivery, particularly for infectious diseases like HIV and COVID-19.

Safety Considerations

While lentiviral vectors offer many advantages, safety is a critical concern. Key safety features include:

• Self-Inactivating (SIN) LTRs: These modifications reduce the risk of insertional mutagenesis by preventing the activation of nearby oncogenes.
• Pseudotyping: Using envelope proteins from other viruses, such as VSV-G, broadens the host range and enhances safety by preventing recombination with wild-type HIV.
• Split Packaging System: The viral components necessary for replication are divided among multiple plasmids, reducing the risk of generating replication-competent lentivirus (RCL).

Also see

• Retroviral vector
• Gene therapy
• CRISPR/Cas9
• Viral vector vaccine