High-Fidelity Cas9 Variants: Engineering Cas9 proteins, such as SpCas9-HF1, eSpCas9, and HypaCas9, that have been modified to reduce non-specific DNA interactions can decrease off-target effects while maintaining on-target efficiency.
Base Editors: Using base editors (e.g., cytosine base editors or adenine base editors) that convert single nucleotides without inducing double-strand breaks can enhance specificity and reduce off-target effects.