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Table 1 Main characteristics of programmable genome targeting domains suitable for directing epigenetic modifiers

From: Synthetic epigenetics—towards intelligent control of epigenetic states and cell identity

  Zinc fingers TAL effectors CRISPR/Cas9
Origin Eukaryotic species Phytopathogenic bacteria Bacterial and archaea species
Type of DNA recognition Protein:DNA Protein:DNA RNP:DNA (Watson-Crick base pairing)
Function of the protein of origin Transcription factors Transcription factors DNA nuclease (inactivated for use in epigenetic editing)
Sensitivity to DNA modification Sensitive to DNA modification Sensitive to DNA modification Not sensitive to DNA modification state
Recognition sequence length Potentially long, but not all sequences can be recognized, size restrictions apply Potentially very long, constraints apply 17–20 bp, requires an adjacent PAM sequence
Specificity/off-target effects Less specific than TALEs Most specific More relaxed sequence recognition than ZF and TALES
Size of protein Variable—depends on length of recognized sequence, one protein unit (approximately 3 kDa) per 3 bp of recognition sequence Variable—depends on length of recognized sequence. Typically 50-70 kDa Holoenzyme (~160 kDa)
Immunogenicity Similar to natural mammalian proteins, potentially low immunogenicity Unknown, needs further investigation Unnatural for mammals, potentially high immunogenicity, needs further studies
Multiplexing Difficult and labour intensive Difficult and labour intensive Easy and possible