22-bp pseudo-palindromic I-CreI DNA recognition sequence (I-CreI site) (I-CreI site)

The 22-bp pseudo-palindromic I-CreI DNA recognition sequence is the specific genomic substrate for the I-CreI homing endonuclease, a member of the LAGLIDADG family originally derived from the chloroplast of Chlamydomonas reinhardtii (Chevalier et al., 2003, PubMed: 12665531). This sequence is characterized by its 22-base pair length and a pseudo-palindromic structure that allows for the precise binding and cleavage by the I-CreI enzyme, creating a staggered double-strand break with 4-nucleotide 3' overhangs (Prieto et al., 2007, PubMed: 17515905). In therapeutic development, this sequence serves as the foundational template for the ARCUS genome editing platform, where the I-CreI protein scaffold is re-engineered to recognize and cleave specific human DNA sequences (Smith et al., 2006, PubMed: 17130138). These engineered nucleases are being investigated for the treatment of various conditions, including chronic Hepatitis B and genetic disorders like primary hyperoxaluria, by facilitating targeted gene disruption or repair (Grizot et al., 2009, PubMed: 19703951). While the I-CreI site offers high specificity, the primary therapeutic challenge involves ensuring that the engineered nucleases do not recognize similar "off-target" sequences in the human genome, which could lead to genotoxicity or chromosomal rearrangements (Paques & Duchateau, 2007, PubMed: 17631277).

Other names

I-CreI recognition siteI-CreI target sequence22-bp I-CreI siteC1234 sequenceHoming endonuclease recognition site

Induction of site-specific double-strand DNA breaks followed by non-homologous end joining (NHEJ) or homology-directed repair (HDR)