Advances in the research of lysovirus and its carrier system

Lentivirus is a type of retrovirus that takes a relatively long incubation time, so it's called a "slow" virus, which Lenti means slow in Latin. It includes human immunodeficiency virus (HIV), cat immunodeficiency virus (FIV), ape immunodeficiency virus (SIV), bovine immunodeficiency virus, etc. The most studied is the HIV-1 lyovirus.
Lentivirus vector is based on the lentivirus
gene
group and is constructed by replacing some of the genes with the desired destination gene. The lysovirus vectors currently in use are mostly
-1
the genome. Compared with the general retrovirus vector, the lysovirus vector has the ability to infect both dividing cells and non-dividing cells and has a wider host range. Lyovirus vectors can also effectively integrate exogenetis genes into host chromosomes for long-lasting expression. In terms of infection ability can effectively infect neuron cells, liver cells, cardiomyocytes, tumor cells, endotrical cells,
stem cells
and other types of cells, but also rarely trigger the body's immune response, can achieve good gene therapy results, with broad application prospects.
with the in-depth study of virus vectors, in order to improve the safety of lysovirus clinical use, the optimization of lysovirus vectors is also being discussed. The development of virulocytic vector has gone through three stages, the first generation of lysovirus carrier system is represented by three-particle system, in the construction of HIV-1 genome packaging, reverse transcription and integration of the required smooth action of the original and coding trans-acting protein sequence separation, respectively, built on three proton expression systems, namely packaging prosurges, envelopes and vector protons. Packaged prosurfics control the expression of all viral structural genes except env under the role of cytomegalovirus (CMV) protons; Using these three kinds of proton co-transfed packaging cells such as human embryonic kidney 293T cells, in the cell clear can harvest only one infection capacity, but no replication ability of lyrovirus particles. The first generation of lysovirus vector system is characterized by the construction of three packaging prosultes, in order to reduce the likelihood of producing a replicable virus, as far as possible to reduce the homogeneity sequence between the three protons, but the packaging protons still retain THE secondary genes. The second-generation lyvirus vector system was improved on the basis of the first generation, removing all dependent genes of HIV from the packaged protons. The removal of these ancillary genes does not affect the titration and infection capacity of the virus, while increasing the safety of the vector. The third-generation lyrovirus vector system adds two more safety features: one is to build its own invigorated lyrovirus vector, that is, to remove the U3 region of 3'LTR, so that the vector loses THE-1 enhancer and pro starter sequence, even if all the viral proteins can not transrecert RNA; Therefore, the third generation of lysovirus carrier system is more secure.
is now widely used in RNA interference studies. Because some types of cell lipids trans-dye less effectively, the half-life of shRNA transferred to cells is short, and the inhibition of gene expression by in-body synthesized siRNA is usually short-lived, so its application is also subject to greater limitations. Using pre-in-body construction of a carrier that can express shRNA, and then packaging it into lyovirus particles that can express shRNA, can directly infect some difficult cells, not only convenient, but also can achieve the long-lasting inhibition effect of gene expression.
The research of zovirus-based zovirus vector has developed to a certain level, so the clinical study of lysovirus as a gene transfer vector has begun, in the laboratory and clinical research, lysovirus has special advantages, especially can infect non-dividing cells, immune response is small. Now clinical studies of HIV-based lysovirus vectors have begun to be applied to humans.
Jikai gene to the market to provide lysovirus products using a safer performance of the third generation of lysovirus vector system, packaging particles to provide the necessary lyviral genes to form the structure of viral particles and packaging functions; The lysovirus titration provided to the market by the Gikai gene can reach 1E-8 TU/mL and can infect the cells of the purpose without enrichment and purification. The cells at the end of the lyvirus infection are then screened with puromycin or by green fluorescence from GFP. Let you on people, mice,
rats,
and other genetic function research more convenient and fast.