Chip-based digital PCR as a direct quantification method for residual DNA in mRNA drugs

Residual exogenous DNA, as common contaminants in biological products, must be monitored and removed to ensure safety. Digital PCR (dPCR) technology is widely applied in DNA quantitative analysis due to high specificity, sensitivity, absolute quantification, etc. Data support is relatively lacking in deciphering the dPCR technology application in residual DNA of mRNA drugs. The current study helped establish the dPCR methods corresponding to two different mRNA vaccines to detect the residual DNA template. The established dPCR methods have a wide linear range, good precision, accuracy, and specificity without being interfered with by encapsulating and demulsifying reagents. The method is simple, rapid, and sensitive which demonstrates that dPCR can directly quantitate other types of risky DNA in mRNA drugs accurately as well.