CRISPR/Cas9-The ultimate weapon to battle infectious diseases?

Abstract

Infectious diseases are a leading cause of death worldwide. Novel therapeutics are urgently required to treat multidrug-resistant organisms such as Mycobacterium tuberculosis and to mitigate morbidity and mortality caused by acute infections such as malaria and dengue fever virus as well as chronic infections such as human immunodeficiency virus-1 and hepatitis B virus. The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system, which has revolutionized biomedical research, holds great promise for the identification and validation of novel drug targets. Since its discovery as an adaptive immune system in prokaryotes, the CRISPR/Cas9 system has been developed into a multi-faceted genetic modification tool, which can now be used to induce gene deletions or specific gene insertions, such as conditional alleles or endogenous reporters in virtually any organism. The generation of CRISPR/Cas9 libraries that can be used to perform phenotypic whole genome screens provides an important new tool that will aid in the identification of critical host factors involved in the pathogenesis of infectious diseases. In this review, we will discuss the development and recent applications of the CRISPR/Cas9 system used to identify novel regulators, which might become important in the fight against infectious diseases.

Staphylococcal Osteomyelitis: Disease Progression, Treatment Challenges, and Future Directions

“…CRISPR technology has gained much attention for its gene editing abilities, mainly in mammalian cells (193,194). However, there has been considerable research into the use of CRISPR for the treatment of infectious diseases (195). Seminal research by Bikard et al demonstrated the potential to use CRISPR/Cas9 in targeting staphylococcal infection by targeting the methicillin resistance gene in S. aureus, making a MRSA isolate susceptible to methicillin once again (196).…”

CRISPR-Cas Biology and Its Application to Infectious Diseases

“…Understanding mechanisms by which bacteria, viruses, fungi, and parasites induce human disease is essential to guide optimal clinical care and rational design of targeted therapies and vaccines. CRISPR-Cas9-based gene editing has been used across diverse pathogens to inform gene and protein contributions to molecular pathogenesis (28). Winter et al employed a CRISPR-Cas9 sgRNA library to elucidate the mechanism by which ␣-hemolysin, a Staphylococcus aureus virulence factor, induces cytotoxicity (29).…”

Roles of microRNAs in T cell immunity: Implications for strategy development against infectious diseases

“…The complex is capable of cleaving the target DNA sequence known as the photospacer guide sequence and the 5′‐NGG‐3′ sequence known as the protospacer adjacent motif (PAM) . This technique can be used in different pathogens such as bacteria, viruses, and parasites to lessen virulence . The use of this system could increase the efficiency of vaccine antigens against infectious diseases and that of cancer immunotherapy in the host .…”