Genetically Modified Phages: Advancements in Human Health

Genetically Modified Phages: Advancements in Human Health

Nexabiome is a UK biotech company that specialises in bacteriophage research with a particular focus on human and animal health applications. Genetically engineered phages are viruses, precisely modified using genetic engineering techniques, that infect and kill specific species of bacteria. These phages can be tailored to target harmful bacteria or specific tissues with exceptional precision, aligning with the goals of personalised medicine and targeted therapies. Their potential impact on human health is significant; they could revolutionise how we treat bacterial infections, overcoming the growing challenge of antibiotic resistance and improving treatment outcomes.

Understanding Genetically Engineered Phages in Human Health

As a result of the antibiotic resistance crisis, bacteriophages have gained traction as a potential alternative to treating bacterial infections. Several case studies have highlighted their potential for various applications. However, they also have limitations, including a very narrow host range, the potential for resistance, and inherent instability. Genetic engineering of phages represents an opportunity to overcome these limitations, enhancing phages’ natural properties while retaining their advantageous natural features.

Genetic modification of phages usually involves gene mutation, gene replacement, or integration of foreign genes to either broaden the host range or enhance the efficacy of phages at targeting bacterial infections. To expand the host range, genes associated with the tail fibre proteins are usually mutated or replaced. To increase the phage’s antimicrobial properties, foreign genes that are harmful to the host are integrated into the host genome. 

Genetic engineering of phages has proven promising, allowing them to be used beyond their natural antimicrobial activity. These engineered phages can disrupt biofilms, deliver antimicrobials, and alter their host range for more targeted antibacterial applications. More intriguingly, they have also found applications in eukaryotes, acting as vehicles for delivering genes and drugs to targeted cells and playing a role in vaccine development and tissue engineering. 

Personalised Medicine: Tailoring Treatments with Genetically Engineered Phages

Personalised medicine is a rapidly evolving field that promises a new age of healthcare where treatments are tailored to the individual. Personalised phage therapy involving genetically engineered phages is playing a significant role in individualised treatment approaches. Phages can be modified to target specific cells, delivering therapeutic molecules directly where they are needed. This precision amplifies the efficacy of treatment and minimises side effects, increasing the chances of successful treatment and improving patient outcomes. Using engineered phages could change how we approach disease treatment and management, making personalised medicine a reality for more patients. Two important uses for genetically modified phages in personalised medicine are in targeted therapies and in treating antibiotic-resistant infections, which we will discuss in the following sections.

Targeted Therapies: Precision Medicine at its Finest

The natural specificity of bacteriophages for targeting host cells makes them great candidates for targeted therapies within precision medicine. Genetically engineering phages further improves their potential by broadening their host range, enhancing their efficacy, or even allowing them to target and deliver therapeutics to specific cells or tissues. The use of phage display-based specific peptides has opened up opportunities for diagnostic tools and targeted drug delivery, which research groups are currently exploring in cancer therapy and diagnostics. 

A recent study highlighted that modified bacteriophages mediated efficient gene delivery to chondrosarcoma cells, resulting in cancer cell death. In one study, researchers packed phages with a siRNA that inhibited lung carcinoma cell growth. Furthermore, another study showed a phage-based system as an effective immunotherapy against solid tumours, highlighting the potential of engineered phages in targeted therapy.

Bacteriophages can also be decorated with imaging dyes and targeted to cancer cells for diagnostic purposes. For example, researchers modified phages to carry a dye and a targeting molecule, allowing them to be internalised by tumour cells. Another study used phages to target and image prostate cancer cells, showing their potential in therapy and imaging.

Overcoming Antibiotic-Resistant Infections with Genetically Engineered Phages

The growing threat of antibiotic-resistant infections is a major concern for global public health. The overuse and misuse of antibiotics have led to the emergence of multidrug-resistant pathogens, making infections harder to treat and increasing the risk of disease spread, severe illness, and death. This crisis has led scientists to explore alternative treatment methods, including genetically engineered bacteriophages. Genetically modified phages can be designed to specifically target and destroy antibiotic-resistant bacteria with exceptionally high efficacy.

This approach is still in its early stages but has shown promise in laboratory settings and has seen some clinical success. One of the most compelling examples is the successful treatment of a Mycobacterium abscessus infection in a teenager with cystic fibrosis using a cocktail of three genetically engineered bacteriophages. This marked the first therapeutic approach to use genetically engineered phages, demonstrating their potential to combat multidrug-resistant pathogens.

Future Directions and Potential Applications

Advances in genetic engineering have expanded phage applications, not only for controlling and detecting bacteria but also as vehicles for therapeutic delivery. Ongoing research is investigating the diverse therapeutic applications of engineered phages, including as vaccine platforms for the control of pathogens such as HIV, but research remains in the early stages. 

Despite the promise, robust clinical evidence supporting the efficacy of phage therapy remains lacking, warranting further research and clinical trials. Moreover, the field faces ethical and regulatory challenges, such as the concern of the uncontrolled release of these engineered bacteriophages into the environment and the absence of established regulatory guidelines for their use in human health. 

Conclusions

The potential implications of genetically engineered bacteriophages for human health are vast. It provides a promising avenue for addressing the global challenge of antibiotic resistance and acts as an exciting new strategy in precision medicine. Moreover, genetic modification of phages opens up possibilities for novel applications that could have far-reaching effects on human health and personalised medicine. However, despite these promising developments, there are still challenges to overcome, and further phage research and clinical testing are necessary to fully understand their potential, ensure their safety and efficacy, and mitigate the risks associated with their use. 

Related Articles