Because of their high efficiency, rapid development, low-cost production, and safe administration, mRNA vaccines are an ideal alternative to traditional vaccine methods. Since 2020, the COVID-19 pandemic has brought mRNA technology into the limelight. Messenger RNA technology is revolutionizing the field of vaccines and precision medicine. However, mRNA therapeutics still have many concerns: their persistence, efficacy, and cytotoxicity are uncontrollable to some extent. However, the technology behind messenger RNA still has a lot of issues. Fortunately, RNAi, a crucial RNA technology that can precisely inhibit gene expression, may assist in resolving this problem. To help overcome this challenge, we employed the method based on co-transfecting mRNA and siRNA, where siRNA can help regulate the signal pathway related to mRNA expression and immune response. At present, the co-transfection techniques are optimized to maximize the transfection efficiency and minimize the cytotoxicity. Moreover, I screened out the gene candidates that can help regulate the efficiency of mRNA transfection in vitro. This project will provide new guidance for the development of mRNA therapeutics.