New Methods for Disease Modeling Using Lentiviral Vectors

Given their capacity to transduce nondividing cells, stable integration in the host genome, and moderate immunogenicity, LVs are optimal tools for in vivo gene delivery. Engineering of LV components and the selection of appropriate administration routes have improved LV target specificity and biosafety. The increasing in vivo applications of LV include gene therapy, transgenesis, cell monitoring, vaccine development, and cell reprogramming. The biosafety features and targeting potential of LVs make them excellent candidates for the design of in vivo disease models. Lentiviral vectors (LVs) transduce quiescent cells and provide stable integration to maintain transgene expression. Several approaches have been adopted to optimize LV safety profiles. Similarly, LV targeting has been tailored through strategies including the modification of envelope components, the use of specific regulatory elements, and the selection of appropriate administration routes. Models of aortic disease based on a single injection of pleiotropic LVs have been developed that efficiently transduce the three aorta layers in wild type mice. This approach allows the dissection of pathways involved in aortic aneurysm formation and the identification of targets for gene therapy in aortic diseases. LVs provide a fast, efficient, and affordable alternative to genetically modified mice to study disease mechanisms and develop therapeutic tools. Lentiviral vectors (LVs) transduce quiescent cells and provide stable integration to maintain transgene expression. Several approaches have been adopted to optimize LV safety profiles. Similarly, LV targeting has been tailored through strategies including the modification of envelope components, the use of specific regulatory elements, and the selection of appropriate administration routes. Models of aortic disease based on a single injection of pleiotropic LVs have been developed that efficiently transduce the three aorta layers in wild type mice. This approach allows the dissection of pathways involved in aortic aneurysm formation and the identification of targets for gene therapy in aortic diseases. LVs provide a fast, efficient, and affordable alternative to genetically modified mice to study disease mechanisms and develop therapeutic tools. nonintegrative, double-stranded DNA viruses without an envelope, which transduce dividing or nondividing cells and can cause respiratory disease in humans. Modified versions of these viruses are used as vectors for gene delivery. virus originally discovered as contaminants of adenovirus preparations. These single-stranded DNA viruses can infect both dividing and nondividing cells and do not cause human disease. pathological dilation of the aorta secondary to an alteration in aortic wall components. Aneurysms can appear at several locations (aortic root, thoracic aorta, and abdominal aorta). Aneurysm rupture has a high mortality rate. circular extrachromosomal genetic material. gammaretroviruses are RNA viruses that express reverse transcriptase and integrase. The reverse transcriptase converts the viral RNA into DNA, and the integrase integrates this DNA integrates into the host cell genome. Gammaretroviruses infect only dividing cells. generation of DNA mutations through the introduction of additional base pairs in the DNA sequence (in the case of LVs, mutations occur through the insertion of viral sequences into the host genome). LVs unable to insert their DNA into the host genome. IDLVs have an inactive integrase (enzyme responsible for integration of viral genetic material into the DNA of the transduced cell). IDLVs give rise to episomes, which are progressively lost with cell divisions, resulting in transient transgene expression. process leading to the development of leukemia. Leukemogenesis is thought to be a multistep process involving structural and functional changes in a series of genes that result in the expansion of malignant cells. genetic disorder that affects connective tissue, mainly due to mutations in the Fibrillin1 gene. The resulting connective tissue alterations lead to a characteristic appearance of MFS patients, who are usually tall, thin, and have long limbs and flexible joints. Patients also frequently have scoliosis and an increased incidence of mitral-valve prolapse and aortic aneurysm, which is the major cause of death in these patients. LVs with unrestricted tropism, which can transduce a variety of cell types. cellular proteins that block key steps in the virus life cycle, such as viral replication. LVs that, after integration into the host-cell DNA, are flanked by LoxP sites recognized by the recombinase Cre. Cre activity leads to recombination and subsequent excision of the viral sequences from host DNA. administration routes used to obtain a general distribution in the body. The route can be enteral (through digestive system) or parenteral (e.g., through intravenous or intraperitoneal injection). modification of viral vector characteristics to achieve preferential transduction or transgene expression in a selected cell type. transport of macromolecules and viral particles across a cell. Transcytosis is a frequent mechanism in ECs, in which the protein albumin is transported through a specialized transcytosis mechanism. transfer of exogenous DNA into a cell by a viral vector. selectivity of a virus for a given host tissue, partially dependent on the interaction of viral surface structures with host-cell surface receptors.