New research opens doors to improved infection treatments
Scientists have developed a groundbreaking method to create phage DNA, paving the way for enhanced infection treatments. This innovative technique enables researchers to construct bacteriophages with entirely synthetic genetic material, allowing for the addition and removal of genes as needed.
The study, led by Professor Graham Hatfull of the University of Pittsburgh, introduces a novel approach to understanding the intricate workings of bacteria-killing viruses. By creating synthetic DNA based on naturally occurring phages that target Mycobacterium (the bacteria responsible for tuberculosis and leprosy), researchers can now explore the functions of individual genes and their impact on phage behavior.
One of the key challenges in phage research has been the technical difficulties associated with synthesizing DNA containing high percentages of G and C base pairs, which are prevalent in Mycobacterium-attacking phages. Traditional methods struggle with these 'high GC' DNA sequences, making it challenging to edit and manipulate phage genomes.
To overcome this hurdle, Hatfull collaborated with experts from New England Biolabs and Ansa Biotech. Together, they developed a process that enables the synthesis of high GC DNA, allowing for the creation of synthetic phage genomes identical to those of BPs and Bxb1, two naturally occurring phages with 40,000 and 50,000 base pairs, respectively.
The team constructed the synthetic DNA in 12 sections and successfully inserted them into a cell, which then followed the new genome's instructions to produce phages. This breakthrough not only enhances our understanding of phage behavior but also holds promise for engineering phages with broader applications in combating antibiotic-resistant bacterial infections.
Phages have co-evolved with bacteria for billions of years, resulting in specialized relationships where one phage targets a specific type of bacteria. However, the exact mechanisms by which phage genomes codify these relationships remain largely unknown. Hatfull's lab, which houses a vast collection of phages, is now better equipped to explore these mysteries and potentially engineer phages with even more diverse applications.
The ability to create entirely synthetic genomes also has significant implications for storage and accessibility. Instead of preserving phages in freezers, researchers envision a future where phage information can be stored and accessed digitally, eliminating the need for extensive phage collections and providing a more efficient and accessible approach to phage research.
