Nano Non-Viral Gene Vector

Gene therapy is the introduction of exogenous normal genes or genes with therapeutic effects into target tissues or target cells through vectors or other means, and appropriate expression to treat diseases. The key of gene therapy is to obtain efficient and safe gene delivery vectors. Vectors for gene delivery are generally classified into viral vectors and non-disease vectors. Viral vectors are the most widely used gene vectors, including retroviruses, adenoviruses, adeno-associated viruses and lentiviruses. The biggest advantage of viral vectors is the high transfection rate, but they also have many disadvantages, such as the difficulty of virus preparation, the limited size of loaded foreign DNA, cytotoxicity, immunogenicity, carcinogenicity, etc., and its immunogenicity And tumorigenicity has not been completely resolved so far. These shortcomings have greatly restricted the clinical application of viral vectors. Although non-viral vectors cannot achieve the extremely high transfection efficiency of viral vectors, non-viral vectors make up for the shortcomings of viral vectors. They have high safety, low immunogenicity, simple preparation, close binding with DNA, and are not immune. The limitation of the size of DNA fragments and the ability to transport plasmid DNA to target cells through targeted modification make it possible for gene therapy to be applied in clinical practice. Nano gene delivery technology uses nanoparticles as carriers to wrap DNA, RNA, etc. in nanoparticles or adsorb on their surface, and couple specific targeting molecules (monoclonal antibodies, etc.) on the surface of the particles to interact with cells through the target molecules. Surface-specific receptor binding allows nanoparticles to enter target cells. Under the action of lysosomes, nanoparticles are degraded to release therapeutic genes, realizing targeted gene therapy. It can protect nucleic acid from being degraded by enzymes, increase the amount of nucleic acid into human cells, enhance its stability in the cell, extend the sustained expression time of genes, help improve cell transfection efficiency, and it is possible to achieve targeting delivery.

Gene Vector

Under physiological conditions, DNA, siRNA, etc. are negatively charged, and it is difficult to combine with the same negatively charged cell membrane and enter the cell without external force or carrier action. At the same time, naked genes are usually easily degraded and are not conducive to targeting cells, while cationic polymer gene carriers can play a good role in compressing, protecting and delivering genes. However, a series of problems will arise when pure cationic polymers are used as carriers in the body. When entering the blood circulation, the surface positive charge of complex becomes an obstacle, because the positively charged complex not only causes the red blood cells to accumulate, but also combines with the plasma components to cause the particles to increase, which is easily affected by the reticuloendothelial system (RES ) Devoured. A pure cationic polymer lacks specificity to tissue cells, and the amount that reaches the target cells is small. The complex needs to pass through the cell membrane of the target cell to enter the human cell; to reach the nucleus further, it has to go through a series of physiological obstacles.

An ideal non-viral gene vector should have the following characteristics: 1. It is safe, low-toxic, has good biocompatibility, is simple to prepare and reproducible, and can be degraded in the body; 2. The vector is targeted; 3 . It can be tightly combined with genes (DNA or siRNA) to protect them from nuclease degradation; 4. It can promote the absorption of genes by cells and help genes escape from lysosomes; 5. The carrier should also have a nuclear localization function, which can promote DNA enters the nucleus. The gene transfection efficiency of non-viral vectors is closely related to the size of the vector. Generally speaking, the smaller the transfected particles, the higher the transfection efficiency. Nano gene carriers are usually made of biocompatible materials, and form nano carrier gene complexes by wrapping or adsorbing nucleic acid molecules such as exogenous DNA. The particle size of nanocarriers is usually between 10~100nm, and its huge specific surface area makes it highly capable of adsorbing, concentrating and protecting DNA. It is also one of the main reasons why nanogene carriers can adsorb and operate foreign genes. Nanoparticles can carry foreign genes into cells through endocytosis due to their small particle size. Nano non-viral gene carriers are divided into organic materials and inorganic materials. Organic materials mainly include liposomes, polyethyleneimine, polylysine, chitosan, dendrimers, etc.; inorganic materials mainly include silica, iron oxide, hydroxyapatite, and gold particles.