Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects

Abstract

Based on engineered or bacterial nucleases, the development of genome editing technologies has opened up the possibility of directly targeting and modifying genomic sequences in almost all eukaryotic cells. Genome editing has extended our ability to elucidate the contribution of genetics to disease by promoting the creation of more accurate cellular and animal models of pathological processes and has begun to show extraordinary potential in a variety of fields, ranging from basic research to applied biotechnology and biomedical research. Recent progress in developing programmable nucleases, such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas-associated nucleases, has greatly expedited the progress of gene editing from concept to clinical practice. Here, we review recent advances of the three major genome editing technologies (ZFNs, TALENs, and CRISPR/Cas9) and discuss the applications of their derivative reagents as gene editing tools in various human diseases and potential future therapies, focusing on eukaryotic cells and animal models. Finally, we provide an overview of the clinical trials applying genome editing platforms for disease treatment and some of the challenges in the implementation of this technology.

Secondary Resistant Mutations to Small Molecule Inhibitors in Cancer Cells

“…One challenge has been the delivery of these therapies. However, with technical advances such as CRISPR [618,619] and nanotechnology [620][621][622][623][624] it is clear that in the near future we will see much more complex forms of cancer treatments.…”

Genomic Medicine: Lessons Learned From Monogenic and Complex Bone Disorders

“…Gene editing in clinical practice has major implications in understanding, treating, and preventing deleterious genetic diseases. There are several tools that allow researchers to modify a specific DNA region such as zinc-finer nucleases (ZFNs) ( 182 ), transcription activator-like effector nucleases (TALENs) ( 183 ), and Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 ( 184 ) [reviewed elsewhere ( 185 , 186 )], among others. Compared to the other editing methods, CRISPR/Cas9 has been positioned as faster, cheaper, more precise, and more efficient in selecting and binding to the target DNA sequence.…”

Therapeutic siRNA: state of the art

“…Small interfering RNA (siRNA), microRNA (miRNA) and inhibitory antisense oligonucleotides (ASOs) are representative molecules used to trigger gene inhibition, whereas plasmid DNA, messenger RNA (mRNA), small activating RNA (saRNA), splicing-modulatory ASOs and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas (CRISPR-associated protein) systems are usually employed to increase or correct target gene expression. [2][3][4] Currently, many therapeutic programs have been explored to treat certain diseases.…”