Hepatitis B RNAi new target: induce similar gene silencing

Hepatitis B RNAi new target: induce similar gene silencing. Hepatitis B RNAi newly developed target, this direction is promising, trying to induce similar gene silencing

RNA interference mechanism refers to small interfering RNAs (siRNAs) or microRNAs (miRNAs), an important cellular process that induces gene silencing at the post-transcriptional level by targeting mRNA. From the perspective of therapeutic prospects in this direction, it is important to recognize that synthetic siRNAs can be delivered to cells and try to induce similar gene silencing, even more ideal than siRNA produced in cells (in situ).

Talking about the newly developed target of hepatitis B RNAi, the future of this direction, trying to induce similar gene silencing

Therefore, current medical scientists regard this RNAi as a powerful tool because it can be used to “shoot down” genes of interest, including those related to hepatitis B virus infection. In some research projects around the world, various expressed RNAi are mainly used to inhibit hepatitis B virus replication, such as pre-miRNA (pre-miR) and short hairpin RNA (shRNAs).

There is also an alternative that has attracted much attention around the world, that is, the use of artificially synthesized RNAi, which is delivered to target cells through artificially synthesized nucleic acid delivery system technologies, such as lipid nanoparticles (LNPs).

One advantage of this method is that chemical modifications of RNAi can be introduced to improve the efficiency of the RNAi mechanism in cells (representative drug: ARB-1467, but ultimately did not reach the laboratory goal). In the process of advancing drug clinical projects based on the direction of RNAi mechanism, researchers around the world pay attention to some detailed views supported by the data, for example, although it is not clear how long the low level of hepatitis B surface antigen should be suppressed, and how long after that Achieve functional healing.

In particular, although the serum hepatitis B surface antigen level and the liver cccDNA level are indeed correlated, this correlation has become less ideal in patients with e antigen-negative chronic hepatitis B. The main reason is that the hepatitis B surface antigen is clearly derived from integrated HBV- DNA expression. In addition, researchers around the world are not yet clear how and what methods to rebuild immunity to hepatitis B virus infection while still maintaining the goal of functional cure.

Another small molecule conjugated anti-HBV siRNA is VIR2218, which is still under development. VIR2218 belongs to triaza-N-acetylgalactose (GalNAc) ligand binding siRNA. This siRNA comes from the parent ALN-HBV. VIR2218 is currently undergoing clinical phase II research.

Although, in preclinical and clinical trials, RNAi drugs for the treatment of chronic hepatitis B virus infection are mainly siRNAs, but global researchers are also concerned that miRNAs are potentially very promising alternatives.

Many studies have shown that miRNAs can play an important role by regulating hepatitis B virus replication and host response. For example, miR-199a-3p and miR-210 have been reported globally. They inhibit viral replication by inhibiting the expression of hepatitis B surface antigen and the expression of the pre-S1 region of the hepatitis B virus genome. Other studies have shown that miR-122 reduces the level of hepatitis B virus core antigen by targeting the highly conserved pgRNA sequence of hepatitis B virus.

After entering 2021, some cancer-related miRNAs in 2020, such as miR-15a, miR-16-1, miR-17-92 cluster, miR-204, miR-1236, etc., are also reported as anti-chronic hepatitis B miRNAs Potential candidate genes for HBV, because they play a key role in inhibiting HBV replication by targeting specific RNA of HBV.

In recent years, in vivo and in vitro studies, the antiviral effect of miR-302c-3p on hepatitis B virus replication has shown that miR-302c-3p can significantly reduce the copy number of hepatitis B virus cccDNA, and by changing the expression and expression of host factors Inhibit HBV transcription, thereby inhibiting the replication of hepatitis B virus and the production of hepatitis B surface antigen.

On September 7, 2020, the scientific journal Viruses, Ganesh Selvaraj Duraisamy, Dattary Bhosale and other scientists once described this: These data show that miR-302c-3p represents a potentially very effective API clue for the treatment of chronic hepatitis B.

On the other hand, miR-802 studies have shown that its overexpression actually promotes the expression of the entire hepatitis B surface antigen and e antigen, while the inhibitory effect of miR-802 is to reduce the expression of hepatitis B surface antigen and e antigen. Therefore, miR-802 has an important influence on the expression and replication of hepatitis B virus. Namely miR-802, may be a new development target for chronic hepatitis B virus infection

(source:internet, reference only)

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