Overview
Colorectal cancer (CRC) ranks among the top deadly cancers globally. While screening methods have significantly reduced death rates, they do come with their own set of challenges. Colonoscopies, although effective in spotting precancerous polyps, are invasive. This invasiveness often leads individuals to delay or avoid screening. In the U.S., only about 70% of adults between 50 and 75 are current with their colonoscopy screenings.
Noninvasive tests like FIT and Cologuard look for shed tumor DNA in stool samples, but their accuracy lags. Simon Leedham, a genetics professor from the University of Oxford, noted that cell-free DNA quickly breaks down in the intestines, impacting test sensitivity.
However, researchers at the University of California, San Diego (UCSD), and several Australian institutions, have proposed a promising alternative. They are developing bioengineered bacteria to detect cell-free DNA from tumors within the digestive tract. This approach was highlighted in a recent study published in Science.
Bioengineered bacteria, specifically Acinetobacter baylyi, show potential for advanced cancer screening. This bacterium can naturally take up external genetic material and integrate it into its genome. Lead author Robert Cooper from UCSD explained, “A. baylyi excels in natural competence, making it ideal for this application.”
The Role of CRISPR-Cas9
To exploit A. baylyi‘s abilities, the team used CRISPR-Cas9. They inserted a mutated version of the KRAS oncogene, commonly found in 27% of CRC cases. They also included the KanR gene for kanamycin resistance. When the engineered bacteria integrate the tumor KRAS gene, KanR activates, indicating successful detection.
In their study, researchers introduced engineered colorectal cancer organoids into mice. They then rectally administered the bacterial biosensors. Cultures from these mice showed that bacteria which integrated the mutated KRAS gene thrived on agar plates treated with antibiotics.
While this method won’t be directly used clinically, Cooper suggests adaptations. Outputs might be detected through urine, blood, or stool samples.
Limitations and Future Prospects
This innovative technique has certain limitations. It appears best suited for cancers of the digestive tract. Tumors in these regions release DNA directly into an environment already full of bacteria, simplifying sampling.
The strategy also relies on predefined mutations. Not all tumors share the same genetic changes. However, CRC typically involves a small set of common mutations, making it an ideal candidate. Scaling to human size might also enhance the technique’s efficacy, according to Cooper, offering more target DNA and fitting more biosensors.
For clinical application, these bacterial biosensors could also aid rapid diagnostics of gut infections. They might progress from mere detection to therapeutic roles. Engineered bacteria could potentially release anti-tumor agents upon detecting target DNA.
This future possibility excites experts like Leedham. He envisions a shift toward “cancer cell ‘seek and destroy’ bacterial therapeutics.”
Key Players and Institutions
The work involves prominent scientists and institutions, contributing to this pioneering research. The team includes:
- Robert Cooper, Jeff Hasty, and other researchers from the University of California, San Diego (UCSD).
- Multiple Australian institutions with notable contributions.
Key contributors to the study each bring unique expertise, enhancing the research’s depth and reliability.
Potential Applications and Innovations
The applications of this technology extend beyond CRC screening. They can revolutionize gastrointestinal cancer diagnosis and treatment. Other potential uses include:
- Non-invasive diagnostics for various digestive tract conditions.
- Personalized medicine based on detecting specific mutations.
- Therapeutic modes, where engineered bacteria deliver targeted treatments.
Bioengineered bacteria offer a flexible and effective solution to existing limitations in cancer diagnosis and therapy.
A Look at Future Developments
Continuing advancements in this field could see widespread clinical applications. Innovations may reduce reliance on invasive procedures like colonoscopies. Researchers aim to refine bacterial biosensors for higher sensitivity and broader use cases.
Furthermore, integrating CRISPR technology into public health strategies can pave the way for more precise and personalized medical interventions. The ultimate goal is to enhance early detection and provide targeted therapies, reducing cancer mortality rates.
Bioengineered bacteria are not just a frontier for cancer detection. They represent a broader shift toward integrating synthetic biology with medical science, addressing complex health challenges with innovative solutions. Researchers continue to explore diverse applications, relationships between bacteria and human health, and the potential for programmable probiotics.
These advancements promise significant strides in improving healthcare outcomes, making diseases like CRC more manageable and treatable. The collaboration between bioengineers, scientists, clinicians, and institutions fosters a robust foundation for this transformative research.
As bioengineered bacterial biosensors move closer to clinical realization, they showcase the intersection of technology and biology, leading to smarter, more responsive healthcare solutions. This ongoing research marks the beginning of a new era in medical science, where the tiniest organisms could hold the key to groundbreaking treatments.
