MNs, ZFNs, TALENs, and CRISPR/Cas systems are promising genome editing tools for treating gene mutation or chromosome rearrangement problems. Chromosome X, the most researched chromosome by genome editing techniques, shows the latter and inspired hopes for hemophilia A therapy. Researchers are also interested in utilizing these approaches to reduce frequent translocations in hematological malignancies. They have also proved highly useful in animal modeling. Lastly, these devices are the topic of several current clinical trials, most of which are in the early stages. CCR5 disruption was ZFN's first clinical use to inhibit HIV from entering cells. This approach allegedly healed one HIV-positive patient. Many clinical trials currently use the same strategy. Moreover, several preclinical investigations employing ZFN-mediated gene editing are being conducted to cure a number of human monogenic diseases. Twelve and 102 Furthermore, in recent years, TALEN technology has improved in terms of robustness, specificity, and fidelity, 15 and new variations of this tool, such as TALE recombinases and single-chain TALE-meganuclease fusions, have emerged.TALENs are also used in clinical research, especially in leukocyte neoplasms, such as the production of CART cells and in two trials to treat HPV-related malignant neoplasms. Unfortunately, owing to a BPDCN patient's death, the TALEN-based clinical investigations for UCART123 were terminated. The CRISPR/Cas system and its various versions have attracted more interest in the realm of epigenome/genome editing because of its simplicity and versatility. In clinical research, CRISPR/Cas9 is mostly employed to treat solid tumors. Nuclease transport, off-target effects, and nuclease efficiency still have problems. Despite the FDA's suspension of two clinical trials, genome editing tool-based products are expected to have a bright future due to the increasing number of trials using CRISPR/Cas9 and other editing technologies. Furthermore, contrary to cell-based therapies and tissue-engineered goods, the expanding number of gene therapy-based products implies that genome editing technologies have a bright future in addressing a wide variety of medical conditions. In particular, products with an in vivo delivery method highlight the tremendous potential these approaches have for direct correction of genetic abnormalities in numerous organs. Examples are Zolgensma, Imlygic, Luxturna, Gendicine, Oncorine and Neovasculgen. However, they are reliant on introducing a correct copy of the defective gene into cells. Recently, in the United States, the first in vivo human CRISPR trial was initiated to remove the IVS26 point mutation in the CEP290 gene to treat LCA10. The outcomes of this experiment, as well as others employing genome editing methods, will definitely have a substantial influence on the future application of these techniques to treat human diseases.
In vivo Genome Editing Therapeutic Approaches for Neurological Disorders: Where Are We in the Translational Pipeline?