Disadvantages
Since the delitto perfetto technique is based on homologous recombination, this process must be functional in the cells for the technique to work. In Saccharomyces cerevisiae, the RAD52 gene is essential for homologous recombination, and thus is required for the delitto perfetto method.
The method is useful only for applications where selectable markers are not necessary. For example, mutagenized yeast strains cannot be used for further genetic analysis such as tetrad analysis. Markers would have to be inserted into the appropriate locus in a separate process.
Read more about this topic: Delitto Perfetto