CRISPR-Cas9 Case Study

Despite the therapeutic advancement, clinical translation of CRISPR-Cas9 faces outstanding challenges, basically in terms of the safety and efficacy of these treatments, translatability of in vivo delivery methods, potential immunogenicity and the delivery vectors used 8.First, a major challenge in therapeutic genome-editing technologies is the potential for off-target effects which mostly result into permanent genetic modification leading to introduction of unwanted mutations.These may impact potential toxicity to the target host 3. Additionally, undesired modifications may lead to the functional loss of a particular gene and also result into reduced fitness of the edited cells. 2. For example, cancer may arise from mutations in tumour suppressor,
In the case where editing imposes a fitness disadvantage, such as the correction of mutated tumor suppressor genes in cancer cells, modified cells would be outcompeted by their diseased counterparts, causing the benefit of treatment to be low. The modification threshold of this final class of diseases would be extremely high requiring many cells to be directly modified and may not be suited for genome editing therapy. Therefore given the current state of technology genome editing therapies are most ideally suited for cases where editing confers a fitness advantage, or where a small change in gene product levels can influence clinical outcomes 2. Additionally, important concern for clinical translation of genome-editing technologies is the immune response to the corrected genes. If a target gene has been misexpressed in tissues due to gene deficiency, possibility is that the proteins produced by the correct copy could induce an adaptive immune response. For exam¬ple, approximately 30% of patients with haemophilia A in a particular study who received protein therapy developed inhibitory antibodies 3. Thus broad application of gene correction technologies may also require further investigation into the development of targeted tolerance