Lentiviruses are used as vectors in gene therapy. The lentivirus vector method makes it possible to insert, modify or delete genes in the organisms where the virus was introduced.
What Is Lentivirus?
Lentiviruses are enveloped RNA viruses with a reverse transcriptase enzyme. They are responsible for causing various diseases like AIDS by injecting their DNA into the host genome. Many viruses are used in research these days, but lentiviruses are unique because they can infect dividing and nondividing. As a result, the potential applications of lentiviruses are wide-ranging. Scientists manipulate the mechanisms of lentivirus infectivity to achieve desired results in gene therapy.
Lentivirus As a Vector
Gene therapy involves using various viruses as vectors to insert the genes of choice into a particular cell or organism. Most retroviruses can not penetrate the nuclear envelope and can’t infect non-dividing cells. On the other hand, Lentiviruses can penetrate the nuclear envelope, and hence, they can be used in gene therapy for cells like neurons that do not divide. Lentiviruses have been used to treat various diseases like diabetes mellitus, prostate cancer, diseases of CVS, and hemophilia.
Applications Of Lentivirus Vector Gene Therapy:
Some parts of their genome are excised to prevent viruses from replicating inside the cells. Another gene is inserted into the viral genome that keeps it permanently attached to the host genome. Lentiviruses are assets of gene therapy that have been used to revolutionize the treatment of the following diseases:
1. Severe Combined Immunodeficiency Disease (SCID):
In 2021, an auto-inactivating lentivirus vector was inserted into a functional ADA gene of hematopoietic and progenitor stem cells. More than 90% of people stayed free of any immune reaction for over 36 months, and the mortality was zero. This innovation is groundbreaking because SCID is a lethal disease.
2. Vascular Transplants:
The third generation lentiviruses have been used and proven effective in venous grafts and coronary bypass. Since the dangerous viral genes are removed, it becomes safer to be inserted into human grafts. The continuous gene expression requires the promoters, which are provided by the scientists through induction of a self-inactivating plasmid and by creating a universal tropism.
3. Chronic Granulomatous Disease (CGD):
In CGD, the mutations in NADPH oxidase of phagocytes result in immune deficiency. Hence, phagocytes deficient in this enzyme can’t phagocytose the infective bacteria resulting in the formation of granulomas. Extensive research and experimentation made it possible to develop a lineage-specific lentivirus vector that expressed a normal CGD protein, which induced white blood cells to form a functional NADPH oxidase.
4. Prostate Cancer:
Lentivirus vector is bound to trastuzumab which causes the viral transformation. The lentivirus vector attaches to androgen-sensitive LNCaP and castration-resistant C4-2 cell lines. By adhering to these cells, lentivirus vectors can slow down or even kill the malignant cells because these cells are responsible for releasing the human epidermal growth factor receptor HER-2.
5. Diabetes Mellitus:
The stem cells targeted by gene therapy create new cells with the genome produced by the viral intervention. The vector targets beta cells of the pancreas to produce more insulin via inducing more insulin-secreting genes. These vectors were cloned by using cytomegalovirus.