Exonuclease I (Exo I)-resistance refers to the ability of a nucleic acid strand, typically single-stranded DNA (ssDNA), to withstand degradation by the enzyme Exonuclease I.
In molecular biology and nucleic acid therapeutics, engineering Exo I-resistance is a key strategy for protecting oligonucleotides, such as like aptamers, antisense oligonucleotides, or rolling circle amplification products, from rapid enzymatic breakdown.