Home Genetics / Genomics CRISPR-Cas9 Gene Editing Complete Protocol
Genetics / Genomics Journal of Visualized Experiments Citable · DOI

CRISPR-Cas9 Gene Editing Complete Protocol

Wei Zhang, MIT · MIT Department of Biological Engineering · 2023
DOI: 10.3791/60954 · View original ↗
Protocol

This protocol details the complete CRISPR-Cas9 gene editing workflow in mammalian cells (HEK293T): gRNA design, plasmid construction, cell transfection, T7E1 cleavage assay for editing efficiency, and Sanger sequencing validation.

Difficulty
intermediate
Total time
~7-10 days
Cell line
HEK293T
Biosafety
BSL-2

Steps

1
gRNA design and off-target analysis

Use CRISPOR or Benchling to enter the target gene sequence and select candidate gRNAs with high on-target score.

⏱ 1-2 days ▶ --:--
2
gRNA annealing and plasmid cloning

Anneal forward and reverse oligos into double-stranded inserts; digest backbone with BbsI; ligate and transform.

⏱ 3-4 days ▶ 04:35
3
Cell transfection

HEK293T cells at 70 to 80 percent confluence; transfect the Cas9-gRNA plasmid with Lipofectamine 3000.

⏱ 2-3 days ▶ 07:06
4
T7E1 nuclease editing-efficiency assay

Extract genomic DNA, PCR-amplify the target locus, digest with T7E1 endonuclease, and quantify Indel frequency on an agarose gel.

⏱ 4-6 hours ▶ 13:40
5
Sanger sequencing validation of Indels

Send PCR products for Sanger sequencing; analyze with the TIDE tool to quantify Indels and validate edits.

⏱ 1-2 days ▶ 18:22
References
Genome editing with CRISPR-Cas nucleases, base editors, transposases and prime editors
Anzalone A.V. et al. · Nature Biotechnology · 2020
DOI: 10.1038/s41587-020-0561-9
Multiplex Genome Engineering Using CRISPR/Cas Systems
Cong L. et al. · Science · 2013
DOI: 10.1126/science.1231143
A Programmable Dual-RNA–Guided DNA Endonuclease in Adaptive Bacterial Immunity
Jinek M. et al. · Science · 2012
DOI: 10.1126/science.1225829
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