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The CRISPR-based genome perturbation opened a new avenue to the genetic screen by providing a toolkit to conveniently change the DNA sequence, transcription and epigenetic modifications . However, it has remained challenging to assay the complex molecular readouts at high resolution and at scale after perturbation. By introducing an A/G mixed capture sequence into the gRNA scaffold, we demonstrated that the gRNA transcripts could be directly reverse transcribed by poly(dT) primer together with the endogenous mRNA, and followed by high-content molecular phenotyping in scRNA-seq. With this method, the CRISPR perturbation and its transcriptional readouts can be profiled together in a streamlined workflow.