CRISPR: From Microbes to Medicine

By Emma Reid

Image by Braňo from Unsplash

Introduction

Microorganisms are one of the most abundant and diverse life forms on Earth—scientists currently estimate that the human body alone is home to about one trillion microbial cells (NSF, 2021). These microorganisms have played a critical role in the development of modern medicine, from antibiotics to vaccines to even genetic therapies. In recent years, scientists have focused on a powerful genetic tool derived from microbial immune systems: clustered regularly interspaced short palindromic repeats or CRISPR. CRISPR has rapidly revolutionized genetic research, and has even offered up new avenues for treating previously incurable genetic diseases in patients.

Overview of CRISPR

In the 1980s, CRISPR was first discovered inside the immune systems of bacteria (Ishino et al., 1987). When a bacterium survives viral infection, fragments of the invading viral DNA are integrated into the bacterial genome. These stored viral sequences enable the bacterium to recognize and defend against future infections more quickly and efficiently than the first time. When the same viral DNA is detected in the bacterium again, CRISPR-associated (Cas) proteins spring into action. The Cas proteins are guided to the virus, where they induce double stranded breaks in the viral DNA. Without properly functioning DNA, the virus dies (Addgene CRISPR History).

Despite its decades-long presence in the scientific community, the use of CRISPR as a gene editing tool was not discovered until the mid-2010s. Researchers Jennifer Doudna and Emmanuelle Charpentier collaborated together to devise a system composed of CRISPR, Cas proteins, and RNA (Jinek et al., 2012). The result yielded a programmable gene-editing system to target specific sections in DNA in complex organisms, such as humans (Addgene CRISPR History).

Figure 1. An overview of target recognition and DNA cleavage for CRISPR/Cas9 systems. The Cas9 protein (blue) is guided to the target sequence (green) in the organism’s genome through guide RNA (red). Cas9 binds to the targeted DNA sequence, where the DNA is unwound and then cleaved at the target site. Cas9 unbinds from the DNA once the cleavage is complete. Figure adapted from Addgene.

Mechanism of CRISPR in Human Cells

The application of CRISPR in human cells is significantly more complicated than in bacterial systems. While bacterial genomes contain millions of base pairs, the human genome contains billions of base pairs. This difference makes it much more difficult to target specific sequences in the human genome—a challenge that has historically limited gene therapy. However, modern CRISPR technology addresses this limitation through its unique molecular and customizable design.

In CRISPR-based gene editing, a Cas protein—most commonly Cas9—is paired with a synthetic guide RNA (gRNA). The guide RNA is engineered by the researchers to be complementary to a specific target DNA sequence within the genome. Once introduced into a cell, the guide RNA directs the Cas9 protein to the desired location in the DNA, where Cas9 creates a double-stranded break. Without the guide RNA present, Cas9 would cut the DNA in a nonspecific pattern. 

In order to stay alive, cells must be able to repair themselves. Because of this, cells possess intrinsic DNA repair mechanisms that are activated following DNA damage. Therefore, after CRISPR-induced cleavage at the specific DNA site, the cell will activate these mechanisms and begin to repair itself. Scientists can exploit these repair processes to alter genetic information to their desired goal.

One scientific approach involves completely removing a certain genetic sequence to deactivate  and disable protein expression of that gene entirely. Another method includes researchers providing a DNA template sequence for the cell to use during repairs, which would insert the desired DNA sequence into the genome. This method can result in eliciting specific phenotypes in the organism to study the function of a specific gene, or replacing mutated genetic sequences with healthy functioning versions (Salanga & Salanga, 2021).The latter is often the goal of CRISPR-based therapies. 

CRISPR and Its Ethical Controversies

Despite its positives, several technical challenges and ethical concerns surrounding CRISPR still remain, including off-target effects, delivery efficiency, and long-term safety. Ethical concerns have also played a major role in shaping the conflict surrounding CRISPR procedures in humans.

In 2018, the announcement of the first genetically edited human embryos brought these concerns to the forefront. This project altered the genome of twin IVF embryos to insert a mutation that would protect the embryos from the HIV virus. The edits made were done using germline editing—a type of genetic editing where the changes are passed from parent to offspring. Germline editing remains controversial in the scientific community for its heritable properties, leaving the ethics of the project in question by many. Although the study resulted in two successful and healthy births, the work was internationally condemned, and several of the researchers involved were later convicted of illegal medical practices (Scientific American, 2020). Despite these criticisms, the project demonstrated the success of embryonic CRISPR/Cas9 editing in human subjects.

This research trial ultimately intensified global discussion regarding the responsible use of gene-editing in humans. Some researchers oppose gene editing entirely, as the novelty of the technology can lead to unpredicted consequences in humans. Others argue that the technology could be the key to preventing devastating genetic diseases before birth. Some middle-ground scientists commonly propose a compromise between the two sides: restricting CRISPR applications to somatic cells—non-reproductive cells—only to ensure that genetic modifications made in an individual are not passed on to future generations without their consent. 

Clinical Progress and Therapeutic Successes

Despite ongoing ethical debates, CRISPR technology has demonstrated significant clinical potential. Multiple human clinical trials for CRISPR-based treatments are currently underway—most with encouraging results. For instance, CRISPR-based therapies have been shown to reduce cholesterol and triglyceride levels by approximately 50% in individuals with inherited lipid disorders (Cleveland Clinic, 2025). Additionally, immunotherapies incorporated with CRISPR have shown improved therapeutic potential compared to traditional cancer treatments by enhancing immune cell targeting of solid tumors and malignant blood cancers (Khan et al., 2016).

In early 2025, a landmark achievement further demonstrated the therapeutic promise of CRISPR. A human infant was successfully treated using a personalized CRISPR-based therapy for severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, a rare and life-threatening metabolic disorder (Musunuru et al., 2025; Children’s Hospital of Philadelphia, 2025). CPS1 deficiency disrupts the urea cycle, preventing the conversion of toxic ammonia into urea in the liver. Once ammonia accumulates, patients experience severe neurological and organ damage, often leading to infant death.

Researchers at the Perelman School of Medicine at the University of Pennsylvania developed a base-editing therapy that precisely targeted the genetic variants responsible for the disorder. The treatment was delivered using lipid nanoparticles designed to transport the CRISPR components to liver cells via the bloodstream. The patient, referred to as KJ, experienced no adverse side effects and demonstrated improved metabolic stability and immune resilience (Musunuru et al., 2025). Ultimately, KJ represents the first human patient to ever receive personalized CRISPR therapy as a medical treatment, making this a revolutionary discovery for clinical progress.

Significance of CRISPR-Based Therapies

Cases such as KJ’s demonstrate how CRISPR introduces alternative treatment options for patients who cannot benefit from conventional medicine. In the case of CPS1 deficiency, the primary treatment option is liver transplantation. However, infants who are often too young and medically unstable to undergo such an invasive procedure are left without access to standard care. But CRISPR offers a minimally invasive option for younger patients, reducing their risk and potential side effects. In addition, CRISPR corrects the underlying genetic cause rather than simply managing symptoms alone as with transplantation. 

More broadly, CRISPR enables a shift toward personalized medicine, in which therapies are tailored to an individual’s unique genetic profile. This approach has the potential to improve quality of life and extend patient survival across a wide range of genetic disorders (Ahmed et al., 2026). Ultimately, CRISPR can become a powerful, life-saving tool for future patients with complex medical diagnoses and unique health circumstances that cannot be treated with standard medical practices.

The Future of CRISPR

Although the technology behind CRISPR is relatively new, its impact on biomedical research and medicine has been transformative. The ability to precisely target and modify disease-causing genes has already reduced symptom severity and improved life outcomes for patients with genetic disorders. 

As the technology continues to evolve, the applications and accessibility of CRISPR are expected to expand even further. Recent innovations include researchers at Stanford University integrating artificial intelligence with CRISPR to improve guide RNA design and prediction of off-target effects (Stanford Medicine, 2025). AI-assisted CRISPR can increase accessibility for scientists with little experience in gene-editing technologies, ultimately making the treatment more accessible for patients. Such advancements may accelerate research, improve patient safety, and broaden the adoption of CRISPR therapies in healthcare. 

Additionally, ongoing clinical trials continue to explore CRISPR’s potential to treat a wide range of rare and common genetic diseases. With the success of KJ’s treatment, researchers are now looking towards applying CRISPR towards diseases such as sickle cell anemia and Huntington's Disease. Even though technical and ethical challenges remain, CRISPR represents one of the most promising tools in modern medicine, offering new hope for conditions once considered untreatable.

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References

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