Genome Editing in Medicine: Tools and Challenges

Violeta Mikštienė,Gunda Petraitytė,Eglė Preikšaitienė

doi:10.15388/amed.2021.28.2.8

Violeta Mikštienė, Gunda Petraitytė + Show 1 more

Open Access

https://doi.org/10.15388/amed.2021.28.2.8

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Abstract

Studies which seek fundamental, thorough knowledge of biological processes, and continuous advancement in natural sciences and biotechnology enable the establishment of molecular strategies and tools to treat disorders caused by genetic mutations. Over the years biological therapy evolved from using stem cells and viral vectors to RNA therapy and testing different genome editing tools as promising gene therapy agents. These genome editing technologies (Zinc finger nucleases, TAL effector nucleases), specifically CRISPR-Cas system, revolutionized the field of genetic engineering and is widely applied to create cell and animal models for various hereditary, infectious human diseases and cancer, to analyze and understand the molecular and cellular base of pathogenesis, to find potential drug/treatment targets, to eliminate pathogenic DNA changes in various medical conditions and to create future “precise medication”. Although different concerning factors, such as precise system delivery to the target cells, efficacy and accuracy of editing process, different approaches of making the DNA changes as well as worrying bioethical issues remain, the importance of genome editing technologies in medicine is undeniable. The future of innovative genome editing approach and strategies to treat diseases is complicated but interesting and exciting at once for all related parties – researchers, clinicians, and patients.

Highlights

Evolution has provided many advantages beneficial to humankind in terms of achieving capabilities allowing to be superior over other species
A perfect example of the latter one is the treatment of spinal muscular atrophy (SMA) which is mainly caused by the deletion of the 7th exon of SMN1 gene
This gene is modified by SMN2, and the main difference between these two genes lies in their DNA sequence: several nucleotide changes in SMN2 gene determine the predominant synthesis of exon 7-free mRNA transcript

Summary

Introduction

Evolution has provided many advantages beneficial to humankind in terms of achieving capabilities allowing to be superior over other species. To extensively understand and precisely treat disorders caused by genome mutations, molecular strategies and tools are necessary This emphasizes the importance of rapid advances in various fields of science and technology. Another direction of biological therapy is the use of RNA oligonucleotides (Figure 1). The treatment of spinal muscular atrophy (SMA) which is mainly caused by the deletion of the 7th exon of SMN1 gene This gene is modified by SMN2, and the main difference between these two genes lies in their DNA sequence: several nucleotide changes in SMN2 gene determine the predominant synthesis of exon 7-free mRNA transcript. The therapeutic oligoribonucleotides are designed to increase the incorporation of exon 7 in SMN2 mRNA and partially rescuing the functional SMN protein [10] This RNA therapy was approved in 2016 (FDA release https://www.fda.gov/news-events/pressannouncements/fda-approves-first-drug-spinal-muscular-atrophy)

Programmable nucleases

Delivering to living cells

Bioethical issues

Immune system and malignant tumors

Approaching hereditary diseases

Acute hepatic porphyria

Gene encoding CAR protein

Sickle Cell Disease

Human Immunodeficiency Virus Infection

Human PapillomavirusRelated Malignant Neoplasm

Findings

Conclusion