In the rapidly evolving landscape of biomedical science, CRISPR-Cas9 technology stands out as a revolutionary tool with the potential to transform the way we combat infectious diseases. This gene-editing system, derived from a natural defense mechanism in bacteria, allows for precise, efficient, and cost-effective modifications to DNA. Its applications span from developing novel therapies for chronic viral infections to creating rapid diagnostic tools, heralding a new era in disease management and personalized medicine.

Overview of CRISPR mechanism (What Is CRISPR?, 2022)

CRISPR: A Brief Overview

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) and its associated protein Cas9 function as a genetic scissor, capable of cutting DNA at specific locations. This precision enables scientists to add, remove, or alter genetic material with unprecedented accuracy. Originally discovered as part of the immune system in archaea and bacteria, CRISPR-Cas9 has been adapted for use in various organisms, including humans, and is now a cornerstone of genetic engineering research (CDM Scientists Develop New CRISPR Gene Editing Platform for Precision, 2024).

Combating HIV with CRISPR

One of the most promising applications of CRISPR technology is in the fight against Human Immunodeficiency Virus (HIV). Traditional antiretroviral therapies (ART) can suppress HIV replication but fail to eliminate the virus from the body. CRISPR offers a potential pathway to a cure by directly targeting and excising the integrated HIV DNA from the host genome.

Recent studies have demonstrated the feasibility of this approach. For instance, researchers have used CRISPR-Cas9 to remove HIV proviral DNA from infected cells in vitro, leading to the suppression of viral replication. Moreover, combining CRISPR-mediated editing of the CCR5 gene, a co-receptor essential for HIV entry into cells, with other therapeutic strategies has shown enhanced resistance to HIV infection. A study published in Scientific Reports highlighted the potential of this combined approach, suggesting a synergistic effect in preventing HIV-1 infections (Ye et al., 2024).

HIV requires the co-receptor CCR5 to infect cells. Deletion of CCR5 by CRISPR-Cas9 inhibits the binding of HIV infected cells (Rajan et al., 2022)

CRISPR-Based Diagnostics: SHERLOCK and DETECTR

Beyond therapeutic applications, CRISPR technology has revolutionized the field of diagnostics. CRISPR-based platforms like SHERLOCK (Specific High-sensitivity Enzymatic Reporter unLOCKing) and DETECTR (DNA Endonuclease Targeted CRISPR Trans Reporter) have been developed for the rapid, accurate, and cost-effective detection of pathogens.

These diagnostic tools leverage the collateral cleavage activity of Cas enzymes to detect specific nucleic acid sequences associated with pathogens. For example, SHERLOCK utilizes Cas13 to detect RNA viruses, while DETECTR employs Cas12 for DNA targets. These systems have been successfully applied in detecting viruses such as Zika, Dengue, and SARS-CoV-2, offering results comparable to traditional PCR methods but with faster turnaround times and minimal equipment requirements (Kaminski et al., 2021).
                  

Image above is an overview of the procedure needed for the DETECTR and SHERLOCK CRISPR diagnostic systems (Kirby et al., 2021).

A Landmark in Personalized Medicine: The Case of KJ Muldoon

The potential of CRISPR in personalized medicine was exemplified in the groundbreaking case of KJ Muldoon, a baby diagnosed with a rare genetic disorder known as carbamoyl phosphate synthetase 1 (CPS1) deficiency. This condition, which impairs the body's ability to eliminate waste nitrogen, is often fatal in infancy (Ungar, 2025).

In a historic medical achievement, a team at the Children's Hospital of Philadelphia and Penn Medicine developed a personalized CRISPR-based therapy tailored to correct the specific genetic mutation causing KJ's condition. The treatment involved delivering the gene-editing components directly to KJ's liver cells, effectively "rewriting" his DNA to restore normal function. Since receiving the therapy, KJ has shown remarkable improvement, marking the first successful use of personalized CRISPR therapy in a human patient (The Daily Beast, 2025).

Challenges and Ethical Considerations

Despite the promising advancements, the application of CRISPR technology in medicine is not without challenges. One significant concern is the potential for off-target effects, where unintended genetic modifications could lead to adverse outcomes. Ensuring the specificity and safety of CRISPR-based interventions remains a critical area of ongoing research.

Ethical considerations also play a pivotal role in the deployment of gene-editing technologies. Issues such as equitable access to treatments, informed consent, and the potential for germline modifications necessitate robust ethical frameworks and regulatory oversight. The scientific community continues to engage in discussions to address these concerns and establish guidelines for responsible use.

How common is CRISPR used

The frequency of CRISPR usage is primarily reflected through patent applications, research publications, and clinical trials, which indicate the level of innovation and practical application. In terms of clinical applications, there are currently 25 CRISPR-based therapies in clinical trials, targeting diseases such as sickle cell anemia, beta-thalassemia, and various genetic disorders (Liu et al., 2023). CRISPR is heavily used in the United States and China, with the US taking the lead. As of 2025, the evidence leans toward the United States and China as the primary locations for CRISPR usage, both in research (patent applications and publications) and clinical applications (trials). The US leads with significant patent activity and a high number of clinical trials, while China follows closely, particularly in research output and emerging trials. Other countries like the UK, Germany, and Japan contribute, but at a lower scale. The frequency of use is increasing, with 25 therapies in trial and a growing number of publications, reflecting the technology's expanding role in global health and biotechnology.

Future Perspectives

The integration of CRISPR technology into the arsenal against infectious diseases heralds a new era in medicine. Ongoing research aims to enhance the specificity and efficiency of CRISPR systems, develop novel delivery methods, and expand its applications to a broader range of pathogens.

As our understanding and refinement of CRISPR continue to evolve, its role in diagnosing, treating, and potentially eradicating infectious diseases is poised to become increasingly significant. The success stories, such as the treatment of KJ Muldoon, underscore the transformative potential of CRISPR and pave the way for future innovations in personalized medicine.

References

    CDM scientists develop new CRISPR gene editing platform for precision. (2024, May 30). College of Dental Medicine. https://www.dental.columbia.edu/news/cdm-scientists-develop-new-crispr-gene-editing-platform-precision-medicine-and-cancer-treatment
    Kaminski, M. M., Abudayyeh, O. O., Gootenberg, J. S., Zhang, F., & Collins, J. J. (2021). CRISPR-based diagnostics. Nature Biomedical Engineering, 5(7), 643–656. https://doi.org/10.1038/s41551-021-00760-7
    Kirby, E. N., Shue, B., Thomas, P. Q., & Beard, M. R. (2021). CRISPR tackles emerging viral pathogens. Viruses, 13(11), 2157. https://doi.org/10.3390/v13112157
    Liu, H., Lv, Z., Zhang, G., Wang, X., Wang, Y., & Wang, K. (2023). Knowledge mapping and current trends of global research on CRISPR in the field of cancer. Frontiers in cell and developmental biology, 11, 1178221. https://doi.org/10.3389/fcell.2023.1178221
    Rajan, A., Shrivastava, S., Janhawi, N., Kumar, A., Singh, A. K., & Arora, P. K. (2022). CRISPR-Cas system: from diagnostic tool to potential antiviral treatment. Applied Microbiology and Biotechnology, 106(18), 5863–5877. https://doi.org/10.1007/s00253-022-12135-2
    The Daily Beast. (2025, May 17). Baby Successfully Treated With First-Ever Personalized Gene Editing Therapy. https://www.thedailybeast.com/baby-successfully-treated-with-first-ever-personalized-gene-editing-therapy/
    Ungar, L. (2025, May 15). Gene editing helped a desperately ill baby thrive. Scientists say it could someday treat millions | AP News. AP News. https://apnews.com/article/crispr-gene-editing-rare-disease-mutation-chop-penn-4ab95afadde97164ae6c2450d79acbf8
    What is CRISPR? (2022, January 7). UMass Chan Medical School. https://www.umassmed.edu/rti/biology/crispr-cas9/
    Ye, L., Wang, J., Beyer, A. I., Teque, F., Cradick, T. J., Qi, Z., ... & Cheng, L. (2024). CRISPR/Cas9 genome editing of CCR5 combined with C46 HIV-1 fusion inhibitor for HIV-1 therapy. Scientific Reports, 14(1), 1626. https://doi.org/10.1038/s41598-024-61626-xNature