Site-specific integration (SSI) in biopharmaceuticals is a modern biotechnological tool, which mainly involves the precise insertion of exogenous DNA sequences into specific locations in the host genome. The advantage of this method is that compared to random integration, it can improve safety, stability, expression efficiency, and insertion efficiency.
In the traditional random integration method, exogenous DNA sequences are usually randomly inserted into any position in the host genome, which poses some risks. Firstly, since the insertion position is not controlled, exogenous DNA sequences may insert into important gene regions, leading to host gene dysfunction, carcinogenesis, and other side effects. Secondly, since the insertion position is random, unexpected changes such as splicing, rearrangement, and deletion are more likely to occur after insertion, resulting in unstable therapeutic effects.
In contrast, SSI in biopharmaceuticals can avoid these risks by directing the insertion of exogenous DNA sequences into specific locations in the host genome. Specific locations are usually safe regions that have little or no impact on gene function, so it can improve treatment safety. In addition, since exogenous DNA sequences are inserted into specific locations, unexpected changes such as splicing, rearrangement, and deletion are avoided in the host genome, thus increasing the stability of therapeutic effects. This also means that the SSI method can reduce the side effects of treatment and improve therapeutic efficacy.
The SSI method can also improve the expression efficiency of exogenous DNA sequences. In the case of random integration, exogenous DNA sequences are usually inserted into a gene within the host genome, and often in a reverse orientation, resulting in insufficient expression of exogenous DNA sequences. In contrast, SSI in biopharmaceuticals can insert exogenous DNA sequences into safe regions, which usually have some regulatory relationships with neighboring genes, thus increasing the expression efficiency of exogenous DNA sequences.
In addition to safety, stability, and expression efficiency, the SSI method in biopharmaceuticals can also improve insertion efficiency. This method can use specially designed nucleic acid modification substances (such as zinc finger nucleic acid, CRISPR/Cas, etc.) to guide DNA insertion to the target position precisely. Therefore, compared with traditional random integration methods, the insertion efficiency of the SSI method is higher, which can save time and resource costs and improve work efficiency. Moreover, SSI can also avoid insertion into gene-silenced regions, thus improving insertion efficiency.
The SSI method in biopharmaceuticals can also solve some problems. For example, for some genetic diseases, the pathogenic genes may be located in important gene regions. The traditional random integration method may cause gene region disorder, thus making effective treatment impossible. However, SSI can precisely insert exogenous DNA sequences into safe regions near the pathogenic gene, thus avoiding gene function disorder and improving therapeutic effects. In addition, SSI can also be used to repair specific gene mutations in the host genome, which is particularly important in the treatment of genetic diseases.
Finally, the SSI method can also play an important role in drug development. Since the insertion position of random integration is uncontrollable, it is difficult to conduct systematic pharmacological evaluations. In contrast, SSI can insert exogenous DNA sequences into specific sites, allowing researchers to evaluate drugs in specific environments. This method can greatly improve the efficiency and success rate of drug development.
