Systems and methods for selective DNA multiple displacement amplification of a DNA mixture

A method of selective DNA multiple displacement amplification (MDA) of a DNA mixture comprising a first population of DNA and a second population of DNA, comprising:

• a) providing a catalytically dead Staphylococcus aureus Cas9 complex (dSaCas9) comprising a dSaCas9 protein or derivative thereof complexed with one or more guide RNAs having selective binding affinity for DNA sequences more present in the first population of DNA compared to the second population of DNA and contacting said Cas9 complex with the DNA mixture under a first reaction condition, said first reaction condition being suitable for binding of the dSaCas9 complex to DNA sequences for which it has a binding affinity, and then
• b) contacting a strand-displacing DNA polymerase with the DNA mixture under a second reaction condition, said second reaction condition being suitable for amplification activity of the strand-displacing DNA polymerase;
• wherein the first reaction condition has a higher free salt concentration than the second reaction condition, wherein the first reaction condition has a free salt concentration of above 50 mM NaCl, and wherein the second reaction condition has a free salt concentration of below 50 mM NaCl.