Engineered cas9 nucleases

2-11. (canceled)

A method of treating a patient, comprising administering to the patient a composition comprising:

• an isolated Staphylococcus pyogenes Cas9 (SPCas9) polypeptide comprising an amino acid substitution, relative to a wild-type SPCas9, at one or more of the following positions:
• D23, D1251, Y128, T67, N497, R661, Q695, and/or Q926, and,
• a pharmaceutically acceptable carrier.

13-30. (canceled)

A fusion protein comprising an isolated Staphylococcus pyogenes Cas9 (SPCas9) polypeptide comprising an amino acid substitution, relative to a wild-type SPCas9, at one or more of the following positions:

• D23, D1251, Y128, T67, N497, R661, Q695, and/or Q926, fused to a heterologous functional domain, with an optional intervening linker, wherein the linker does not interfere with activity of the fusion protein.

(canceled)

(canceled)

45-88. (canceled)

A method of editing a population of double stranded DNA (dsDNA) molecules,

• the method comprising contacting the dsDNA molecules with an isolated Staphylococcus pyogenes Cas9 (SPCas9) polypeptide comprising an amino acid substitution, relative to a wild-type SPCas9, at one or more of the following positions:
• D23, D1251, Y128, T67, N497, R661, Q695, and/or Q926, and a guide nucleic acid having a region complementary to a target sequence of the dsDNA molecules, whereby a plurality of the dsDNA molecules is edited.