The first method to detect A-to-I RNA modifications, developed in 1997, was inosine-specific cleavage. RNA samples are treated with glyoxal and borate to specifically modify all G bases, and subsequently enzymatically digested to by RNase T1, which cleaves after I sites. The amplification of these fragments then allows analysis of cleavage sites and inference of A-to-I modification.
. It was used to prove the position of inosine at specific sites rather than identify novel sites or transcriptome-wide profiles.