For cell line engineering, can you design gRNAs to exons and introns?

Yes, gRNAs are designed to exons or introns depending on what is more appropriate for the project. For knockout projects we aim to design gRNAs to conserved exons in the first third of the gene. For knock-in projects where a donor is required to introduce a change in the coding sequence, gRNAs are designed near to the required change in the exon. If the gRNA targets in an exon, we may also introduce silent mutations in the knock-in donor to disrupt the gRNA target site or PAM site, in order to prevent re-cutting of the targeted allele. Depending on gene structure, it may be possible to make a knock-in using a gRNA in an intron. For example, the gRNA could be in an intron distal to that in which an antibiotic resistance marker is located. This would have an impact on targeting frequency, and would require modification of the intronic sequence to prevent re-cutting of the targeted allele, but it would mean that exonic silent mutations would not be required.