The article discusses the advancements in targeted nonviral delivery of CRISPR-Cas genome editors for in vivo applications. It highlights the importance of delivering these editors specifically to desired cell types, tissues, or organs to enhance safety and efficacy. The authors review two main strategies: preassembled ribonucleoproteins (RNPs) and mRNA-encoded Cas nuclease with a separate sgRNA. Both methods offer transient editor lifetime and potential streamlined manufacturing, addressing the safety concerns associated with viral vector-mediated delivery. The article also explores various methods for targeted delivery, including physical isolation of cells for ex vivo delivery, direct injection of nanoparticles, and the use of synthetic and biologically inspired nanoparticles. These approaches aim to overcome the limitations of viral vectors, such as immunogenicity and off-target effects, and enable more precise and efficient genome editing in vivo. The authors emphasize the need for further development of targeted delivery technologies to expand the therapeutic applications of CRISPR-Cas genome editing.The article discusses the advancements in targeted nonviral delivery of CRISPR-Cas genome editors for in vivo applications. It highlights the importance of delivering these editors specifically to desired cell types, tissues, or organs to enhance safety and efficacy. The authors review two main strategies: preassembled ribonucleoproteins (RNPs) and mRNA-encoded Cas nuclease with a separate sgRNA. Both methods offer transient editor lifetime and potential streamlined manufacturing, addressing the safety concerns associated with viral vector-mediated delivery. The article also explores various methods for targeted delivery, including physical isolation of cells for ex vivo delivery, direct injection of nanoparticles, and the use of synthetic and biologically inspired nanoparticles. These approaches aim to overcome the limitations of viral vectors, such as immunogenicity and off-target effects, and enable more precise and efficient genome editing in vivo. The authors emphasize the need for further development of targeted delivery technologies to expand the therapeutic applications of CRISPR-Cas genome editing.