The authors have declared that no competing interests exist.
Gene therapy has entered a new era with the dawn of CRISPR/Cas9 technology which though were always available in nature but rediscovered to tame into a real-tlife genome editing tool. With the modernization upsurge and changes in ways the “homo sapiens” survived on this planet from hunger to current era of exuberance has led to multiple metabolic issues like type-2 diabetes. Notwithstanding the rapid emergence of medication to suppress the hyperglycemia and insulin resistance associated with this menace, need has definitely emerge to find more personalized and curative dimensions to therapeutics of type-2 diabetes mellitus. Gene therapy is one more addition to Type-2 Diabetes Mellitus (T2DM) therapy, where multiple options have emerged in the shape of microRNA, direct knocking out of cellular structures like proteins and enzymes and very recently the precision nucleases associated with CRISPR technologies. This mini-review attempt to summarize some of the recent examples of gene therapy with major focus on CRISPR/Cas technologies.
The world struggles with the current onslaught of metabolic diseases with type-2 diabetes mellitus (T2DM) leading the race with more 451 million people currently living with the disease.
In pursuit of pre-existing technologies using nucleases like Transcription activator like effector nucleases (TALEN), Zinc Finger Nucleases (ZFNs) a need was realized for more powerful, efficient and clinically acceptable tools for genome editing where CRISPR-Cas technology appear as hope and provided multiple avenues for clinical application.
Over the last five years the technology has undergone major modifications from cellular entry modes, nucleases function, optimizing the role of sgRNA and repair mechanisms for new insert all leading to reducing in various off-target effects, making the biotechnology more efficient and cytotoxicity. However, the basic mechanism has not changed.
Literature data search through PubMed and Cochrane library provided only 18 articles dealing directly or indirectly with use of CRISPR Cas technology in management of type-2 diabetes mellitus indicating that a detailed systematic review on the subject is not yet possible. However, we did found some preliminary work related to CRISPR Cas techniques experimentation in animal subjects with type-2 diabetes mellitus. Chao et al (2019) in a proof of concept animal study demonstrated that Non- Liposome Cas9-SgRNA (NL@Cas-RNP) CRISPR payload carrier for inhibiting DPP-IV to boost incretin effect in comparison to DPP-IV inhibitors found the former to be superior in reducing hyperglycemia, providing higher GLP-I levels and reduce insulin resistance with minimal off target effects on hepatocytes and kidneys.
The “aye and nay” of gene therapy utilizing CRISPR/Cas technology are questioned by every day more often than ever. We just can’t spiritualize the CRIPR T2DM promise home till we do not elucidate the wholesome interactive association between nano technology’s offshoots and spinoffs. The CRISPR/Cas technology, though climbing the staircase to glory and optimization in pursuit of personalized and curative medicine for T2DM in specific, still the downsides of the techniques including off-target mutagenesis (OTMs), the need for improvising delivery payload into cellular structures and overall effectiveness are key impediments to clinical application.
CRISPR/Cas technologies present a real promise for the life-long pathology of type-2 diabetes mellitus; however, research only seems exuberant by scarcity of data on the subject and needs major efforts for long-term animal trials on the subject. It is anticipated that CRIPSR/Cas techniques have the futuristic potential to provide long, most beneficial, cost-effective and side-effect free personalized therapeutics for this incoming plague haunting mankind.