Lentiviral vector in gene therapy
Lentiviruses are a family of viruses that are responsible for diseases like AIDS, which infect by inserting DNA into their host cells' genome.
Lentiviruses also have a viral envelope with protruding glycoproteins that aid in attachment to the host cell's outer membrane.
The virus contains a reverse transcriptase molecule found to perform transcription of the viral genetic material upon entering the cell.
The lentiviral RNA and the viral proteins then assemble and the newly formed virions leave the host cell when enough are made.
[citation needed] HIV-derived lentiviral vectors have been widely developed for their ability to target specific genes through the coactivator PSIP1.
Equine infectious anemia virus in particular has been shown to perform somewhat better than HIV-1 in hematopoietic stem cells[13] Historically, lentiviral vectors included strong viral promoters which had a side effect of insertional mutagenesis, nuclear DNA mutations that affect the function of a gene.
More practically, gammaretroviruses have an affinity for integrating themselves near oncogene promoters, bringing forward an adverse risk of tumors.
Such a response can reduce the efficiency of adenoviral vector therapies and can result in adverse reactions such as inflammation of tissues.
[20] The ADA deficient variant of severe combined immunodeficiency (SCID) was treated highly successfully in a multi-year study reported in 2021.
A self-inactivating lentiviral vector, EFS-ADA LV, was used to insert a functional ADA gene in autologous CD34+ hematopoietic stem and progenitor cells (HSPCs).
The researchers accomplished this by the addition of self-inactivating plasmids and creating a more universal tropism by pseudotyping a vesicular stomatitis virus glycoprotein.
The viral vector's responsibility was to increase the production of a functional NADPH oxidase gene in these phagocytic cells.
These two cells are primarily responsible for secretion of excess human epidermal growth factor receptor 2 (HER-2), which is a hormone linked to prostate cancer.
Researchers caused the specificity of the vector by manipulating the Fab region of the viral genome and pseudotyped it with the Sindbis virus.
The vector targets the haematopoietic cells in order to increase the amount of factor VIII, which is affected in haemophilia A.
The vector targets the cells within the pancreas to add insulin secreting genes to help control diabetes mellitus.
Studies of lentiviral gene therapy have been conducted on patients with advanced Parkinson's disease[28] and aging-related atrophy of neurons in primates.
