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New progress of non-viral delivery system for gene therapy of liver disease

2017-02-13 来源:转载自第三方
13 February 2017
  Recently, "Cell Research" published a paper entitled "A non-viral CRISPR/Cas9 delivery system for therapeutic gene targeting in vivo" [1], the paper developed a new CRISPR/Cas9 delivery system, which can deliver CRISPR/Cas9 to the liver in vivo and target cleavage of pathogenic genes under the guidance of single-stranded RNA (sgRNA) to achieve the goal of treating liver disease.
  Gene therapy gradually rise in the last century 90's, it refers to the normal gene into the target cells to correct or compensate for genetic defects and abnormalities caused by the disease, in order to achieve therapeutic purposes. CRISPR/Cas9 is a DNA scissor system found in bacteria, is based on Cas9 protein and guide RNA (gRNA) as the core composition, is the most studied type. Because of its highly specific DNA cut and editing ability, it has been widely used in the field of scientific research. The presence of existing CRISPR/Cas9 in vivo delivery is through the use of adenovirus expression system to express Cas9 and guide RNA, but it has the disadvantages of the lack of targeting, high immunity itself, and the virus in the body have a certain probability of recombinant mutation, and possible long-term side effects and other issues.
  Researchers have developed a new lipid nanoparticle system that can encapsulate Cas9 protein mRNA and single-stranded RNA and deliver it to the liver in vivo and cut for specific pathogenic genes. To test the actual effect of the new lipid nanoparticle system developed, the study group selected the hepatitis B virus (HBV) genome as an exogenous target to test this new drug delivery system. Because there are about 350 million people are infected with hepatitis B virus around the world, and in China it is a serious social problem. China's hepatitis B virus infection rate is about 60%~70%; hepatitis B surface antigen carrying rate is about 7.18%, there are about 93 million people carrying hepatitis B virus the country, of which about 20 million cases of chronic hepatitis B patients. The Hepatitis B virus is difficult to completely remove, the main reason is that its genome in a form of covalent closed-loop DNA, clinically used to treat chronic hepatitis B commonly used drugs are: interferon-α, pegylated interferon-α, Mitfen, and adefovir dipivoxil, entecavir, tenofovir, etc., these existing treatment can not touch cccDNA.
  It was found that at the cellular level, Cas9/sgRNA encapsulated by this new lipid nanoparticle (LNP) could effectively cut HBV cccDNA and Pcsk9 genes in cells and effectively down-regulate the expression of HBV-related antigens. The results of animal experiments showed that the expression of Cas9/sgRNA was delivered to the liver, and the expression of Cas9 protein was the highest after 6 hours of tail vein injection, then decreased gradually and disappeared after 24 hours. In the liver, the delivered Cas9/sgRNA can effectively and specifically cleave the internal and external gene sequences, thereby reducing the expression of the relevant protein. A single injection can effectively reduce the expression of hepatitis B virus more than 50%.
  This new type of lipid nanoparticle delivery system has opened up a new way in clinical practice for this powerful gene editing tool CRISPR/Cas9. This exciting result has brought the dawn to patients with liver disease and is important for the future clinical study of CRISPR/Cas9 systems.
[1] Chao Jiang, Miao Mei, Bin Li, et al. A non-viral CRISPR / Cas9 delivery system for therapeutic gene targeting in vivo. Cell Research, doi: 10.1038 / cr.2017.16.
Edited by the Editorial Office of Suzhou Yacoo Science Co., Ltd.