Applications of CRISPR-Cas9 for advancing precision medicine in oncology: from target discovery to disease modeling

Abstract

The clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9) system is a powerful tool that enables precise and efficient gene manipulation. In a relatively short time, CRISPR has risen to become the preferred gene-editing system due to its high efficiency, simplicity, and programmability at low costs. Furthermore, in the recent years, the CRISPR toolkit has been rapidly expanding, and the emerging advancements have shown tremendous potential in uncovering molecular mechanisms and new therapeutic strategies for human diseases. In this review, we provide our perspectives on the recent advancements in CRISPR technology and its impact on precision medicine, ranging from target identification, disease modeling, and diagnostics. We also discuss the impact of novel approaches such as epigenome, base, and prime editing on preclinical cancer drug discovery.

Therapeutic applications of CRISPR/Cas9 mediated targeted gene editing in acute lymphoblastic leukemia: current perspectives, future challenges, and clinical implications

“…The pegRNA not only specifies the location of the edit, but also carries new genetic instructions to be installed at that location ( Zhao et al, 2023 ). Although prime editing has allowed specific gene modification in various cell types ( Kim et al, 2021 ), its low editing efficiency ( Ravichandran and Maddalo, 2023a ) and the lack of an efficient in vivo delivery system remains crucial challenges for its implementation ( Zhao et al, 2023 ).…”

“…Finally, the use of CRISPR has facilitated the identification of critical targets for leukemogenesis that can guide research in the development of new therapeutic approaches ( Akram et al, 2022 ). The CRISPR activation or inhibition systems (CRISPRa/i) have accelerated the discovery of genes linked to cellular reprogramming by rapidly identifying genetic targets ( Ravichandran and Maddalo, 2023b ). CRISPRa is a modified version of CRISPR that utilizes a catalytically inactive (d) Cas9 fused with a transcriptional effector to activate target gene expression.…”

The Current Situation and Development Prospect of Whole-Genome Screening

“…Researchers routinely apply high-throughput screening techniques to identify genes that influence a specific phenotype in an unbiased fashion. The application areas of genetic screening technology extend beyond large-scale functional screenings, such as therapeutic applications, characterizing functional distal enhancers, targeted reprogramming of lineage specification, generation of induced pluripotent stem cells, and reversal of HIV latency [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ]. In addition to traditional screening techniques, including RNAi and the overexpression of cDNA/ORF, the simple and efficient gene-targeting capacity of clustered regularly interspersed short palindromic Repeats (CRISPR) has been harnessed to functionally screen a large number of genes at the same time.…”