Much　progress　has　been　made　in　the　biosensor　area　with　the　prosperity　and　development　of　nucleic　acid　nanotechnology　and　molecular　biology.　Especially,　the　advances　made　in　dynamic　DNA　nanotechnology　and　the　increasing　sophistication　of　toehold-mediated　strand　displacement　reactions　have　put　new　energy　into　nucleic　acid-based　biosensor　designs.　The　exposure　of　the　gene-editing　ability　of　clustered　regularly　interspaced　short　palindromic　repeats　(CRISPR)　associated　proteins　(Cas)　has　also　greatly　revolutionized　the　way　nucleic　acid　can　be　operated　in　biosensing　systems,　providing　versatile　strategies　for　signal　handling.　Hence,　in　this　review,　we　will　discuss　the　application　of　these　two　technologies　as　the　expanded　tools　for　nucleic　acid-based　biosensors　and　focus　on　their　strategies　governing　signal　transduction.　Besides,　technologies　like　DNA　computing　and　deep　learning　approaches　which　flashed　in　nucleic　acid　biosensors　very　recently　are　also　discussed　in　the　perspective　and　outlook　part.　©　2023　Elsevier　B.V.