There is considerable interest in applying gene-editing methods to the treatment of diseases with a genetic component. However, there are multiple challenges associated with this approach. An effective treatment would require editing of a large number of target cells, which in turn would require an effective method of delivery and a great level of tissue specificity.
As of 2019, prime editing looks promising for relatively small genetic alterations, but more research needs to be conducted to evaluate whether the technology is efficient in making larger alterations, such as targeted insertions and deletions. Larger genetic alterations would require a longer RT template, which could hinder the efficient delivery of pegRNA to target cells. Furthermore, a pegRNA containing a long RT template could become vulnerable to damage caused by cellular enzymes. Prime editing in plants suffers from low efficiency ranging from zero to a few percent and needs significant improvement.
Some of these limitations have been mitigated by recent improvements to the prime editors, including motifs that protect pegRNAs from degradation. Further research is needed before prime editing could be used to correct pathogenic alleles in humans. Research has also shown that inhibition of certain MMR proteins, including MLH1 can improve prime editing efficiency.