C Billard, J Fluss, B Ducot, L Bricout, G Richard, J Ecalle, A Magnan, J Warszawski, J Ziegler
[Deficits in reading acquisition in primary school: cognitive, social and behavioral factors studied in a sample of 1062 children]
Revue d'epidemiologie et de sante publique
crisprcas nucleases system widely considered important tool genome engineering however current methods predicting onofftarget effects designing guide rna grna rely purely datadriven approaches focus solely systems thermal equilibrium properties nonetheless experimental evidence suggests process kinetically controlled rather equilibrium study utilized vast amount available data combined random forest supervised ensemble learning algorithm free energy landscape analysis investigate kinetic pathways rloop formation crisprcas9 system intricate molecular interactions dna cas9 ruvc hnh domains study revealed novel threestate kinetic mechanism b unfolding activation state rloop crucial kinetic determinant key predictor offtarget cleavage efficiencies c nucleotides positions 13 16 kinetically critical nucleotides results provide biophysical rationale design kinetic strategy enhancing crisprcas9 gene editing accuracy efficiency