LITERATURE UPDATE
detection methods. Furthermore, a critical analysis of the clinical applications, advantages, disadvantages, challenges and prospects of the CRISPR-Cas system is provided.
CRISPR-Cas based diagnostic tools: Bringing diagnosis out of labs Chhipa AS, Radadiya E, Patel S. Diagn Microbiol Infect Dis. 2024 Jun;109(2):116252. doi: 10.1016/ j.diagmicrobio.2024.116252.
Timely detection is important for the effective management of infectious diseases. Reverse transcription polymerase chain reaction (RT-PCR) stands as the prime nucleic acid-based test that is employed for the detection of infectious diseases. The method ensures sensitivity and specificity. However, RT-PCR is a relatively expensive technique due to the requirement of costly equipment and reagents. Further, it requires skilled personnel and established laboratories that are usually inaccessible in underdeveloped areas. On the other hand, rapid antigen- based techniques are cost effective and easily accessible, but are less effective in terms of sensitivity and specificity. CRISPR-Cas systems are advanced diagnostic tools that combine the advantages of both PCR and antigen based detection techniques, and allows the rapid detection with high sensitivity/ specificity. The present review aims to discuss the applicability of CRISPR-Cas based diagnostic tools for the infectious disease detection. The review further attempts to highlight the current limitations and future research directions to improve the CRISPR-based diagnostic tools for rapid and effective disease detection.
Therapeutic Potential of CRISPR/ Cas in Hashimoto’s Thyroiditis: A Comprehensive Review Upreti A, Mukherjee S. Curr Gene Ther. 2024;24(3):179–92. doi: 10.2174/ 0115665232266508231210154930.
Hashimoto’s thyroiditis (HT) is a commonly occurring illness of autoimmune endocrine origin. It is usually present in the paediatric age group along with other well-known diseases, such as type 1 insulin-dependent diabetes. The defining feature of this disease is the immune-- mediated attack on the thyroid gland resulting in the destruction of thyroid tissues and cells. Given that HT frequently affects family members, it is well-recognised that individuals are genetically predisposed to this disease. Patients with HT also display a significantly increased risk for several different cancers, justifying the eminent
need for the development of therapies for managing and treating HT. Gene editing has made several advancements in the field of molecular biology and has turned out to become a promising approach to correct several autoimmune diseases. Currently, CRISPR/ Cas, a nuclease-based editing technique, is publicised as a promising tool for curing several genetic diseases and cancers. However, very limited research has been conducted as of now on autoimmune disease management and cure via CRISPR/Cas technique. This review provides an account of the potential candidate genes associated with Hashimoto’s thyroiditis, and only a few animal and human models have been generated via the CRISPR/Cas gene editing technique. Mouse models of autoimmune thyroiditis generated through the CRISPR/Cas gene editing technique by targeting the candidate genes will provide a deeper insight into the pathophysiology of HT and further pave the way for the immunomodulation of HT via gene editing.
Application of CRISPR-cas-based technology for the identification of tuberculosis, drug discovery and vaccine development
Shi L, Gu R, Long J, Duan G, Yang H. Mol Biol Rep. 2024 Mar 29;51(1):466. doi: 10.1007/s11033-024-09424-6.
Despite being the only globally licensed prophylactic vaccine, Bacillus Calmette- Guérin (BCG) has multiple deficiencies, and effective diagnostic and therapeutic options are limited. Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas (CRISPR-associated proteins) is an adaptive immune system that is found in bacteria and has great potential for the development of novel antituberculosis drugs and vaccines. In addition, CRISPR-Cas is currently
recognised as a prospective tool for the development of therapies for TB infection with potential diagnostic and therapeutic value, and CRISPR-Cas may become a viable tool for eliminating TB in the future. Herein, the authors systematically summaris the current applications of CRISPR-Cas-based technology for TB detection and its potential roles in drug discovery and vaccine development.
CRISPR-Cas in Pseudomonas aeruginosa provides transient population-level immunity against high phage exposures Watson BNJ, Capria L, Alseth EO et al. ISME J. 2024 Jan 8;18(1):wrad039. doi: 10.1093/ismejo/wrad039.
The prokaryotic adaptive immune
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system, CRISPR-Cas (clustered regularly interspaced short palindromic repeats; CRISPR-associated), requires the acquisition of spacer sequences that target invading mobile genetic elements such as phages. Previous work has identified ecological variables that drive the evolution of CRISPR-based immunity of the model organism Pseudomonas aeruginosa PA14 against its phage DMS3vir, resulting in rapid phage extinction. However, it is unclear if and how stable such acquired immunity is within bacterial populations, and how this depends on the environment. Here, the authors examine the dynamics of CRISPR spacer acquisition and loss over a 30-day evolution experiment and identify conditions that tip the balance between long-term maintenance of immunity versus invasion of alternative resistance strategies that support phage persistence. Specifically, they find that both the initial phage dose and reinfection frequencies determine whether or not acquired CRISPR immunity is maintained in the long term, and whether or not phage can coexist with the bacteria. At the population genetics level,
emergence and loss of CRISPR immunity are associated with high levels of spacer diversity that subsequently decline due to invasion of bacteria carrying pilus- associated mutations. Together, these results provide high resolution of the dynamics of CRISPR immunity acquisition and loss and demonstrate that the cumulative phage burden determines the effectiveness of CRISPR over ecologically relevant timeframes.
An Antibody-CRISPR/Cas Conjugate Platform for Target-Specific Delivery and Gene Editing in Cancer Yang S, Im SH, Chung JY et al. Adv Sci (Weinh). 2024 Mar 29:e2308763. doi: 10.1002/advs.202308763.
The CRISPR/Cas system has been introduced as an innovative tool for therapy, but achieving specific delivery to the target has been a major challenge. Here, an antibody-CRISPR/Cas conjugate platform that enables specific delivery and target gene editing in HER2-positive cancer is introduced.
The CRISPR/Cas system by replacing
specific residues of Cas9 with an unnatural amino acid is engineered, that can be complexed with a nanocarrier and bioorthogonally functionalised with a monoclonal antibody targeting HER2. The resultant antibody-conjugated CRISPR/ Cas nanocomplexes can be specifically delivered and induce gene editing in HER2-positive cancer cells in vitro. It is demonstrated that the in vivo delivery of
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