Sequenceselective

Sequence-selective describes a property of molecules or processes that preferentially recognize or act on specific nucleotide sequences or motifs, while showing reduced interaction with non-target sequences. This selectivity enables targeted manipulation or detection of genetic material.

The basis of sequence selectivity often lies in direct base-specific contacts between a protein or molecule and the nucleic acid, shape and electrostatic complementarity, or the need for adjacent sequence elements such as a protospacer adjacent motif. In practical terms, sequence-selective reagents bind to or modify only certain sequences, leaving other sequences largely unaffected. This specificity is fundamental to reducing off-target effects in genetic and diagnostic applications.

Contexts in which sequence selectivity is important include molecular biology, biotechnology, and chemical biology. Examples range from restriction endonucleases that cleave at particular motifs, to CRISPR-Cas systems guided by RNA to target matching sequences, to DNA methyltransferases that modify specific sites. Other instances involve sequence-selective DNA-binding proteins such as zinc finger domains or transcription activator-like effectors, as well as aptamers and small molecules designed to recognize defined nucleic acid sequences. The concept also appears in sequencing technologies and nucleic acid-based therapeutics, where precision targeting of sequences is key.

Applications of sequence selectivity include gene editing, molecular diagnostics, and targeted therapeutics, as well as research tools for studying DNA–protein interactions. Limitations often involve off-target activity, dependence on adjacent sequence context, and challenges in achieving uniform performance across diverse sequences. Ongoing developments focus on improving accuracy, expanding targetable motifs, and reducing unintended effects.