Alimitation of retrovirus-mediated gene transfer is that

The answer is Retroviruses integrate DNA randomly in the genome. While retroviruses integrate their DNA permanently in their host genome, hence a good tool for gene therapy, its risk of inserting DNA at an unintended location on target genome can cause insertional mutagenesis. This mutation can cause activation of oncogenes hence lead to tumor growth.

substitution is the answer in this case