Many people have experienced E. coli infection, which is primarily seen as uncomfortable and unpleasant. But for some patients, such as those with leukemia, there is a risk of the bacteria moving into the bloodstream. In these cases, E. coli infection is often fatal. The mortality rate is 15-20%.
The predominant treatment for such infections is the use of antibiotics that have adverse effects on the patient’s microbiome, which play a major role in our physical and emotional health, and other side effects. Furthermore, increasing problems with antibiotic resistance make such treatments less effective in treating infections.
An international team of scientists has now designed the first published CRISPR-based candidate (see fact box) for a drug that targets coli directly and leaves the microbiome intact. new paper in Nature Biotechnology Entitled “Phage engineered with antibacterial CRISPR-Cas technology selectively reduces phage coli The burden in mice’ describes the drug candidate’s development to a point where it is ready for human testing.
Making extensive use of synthetic biology, the team designed four bacterial viruses that use CRISPR technology to precisely kill unwanted bacteria.
says Morten Otto Alexander Sommer, professor at DTU Bios-founder of SNIPR Biome, and lead author of the paper.
The work was carried out in collaboration with JAFRAL (Slovenia), JMI Laboratories (US), and the Division of Infectious Diseases at Weill Cornell Medicine (US).
Targeted engineering phages coli
The team, which is based out of SNIPR Biome, screened a library of 162 naturally occurring bacteriophages (viruses that kill specific bacteria; see fact box). They found that eight of these phages showed promising results in targeting coli. They then engineered the phages through gene editing to improve their targeting ability coli.
A mixture of four of these phages, which they named SNIPR001, very effectively targeted bacteria in biofilms and reduced the number of coli in a way that outperformed naturally occurring phages. Furthermore, they showed that the mixture of phages was well tolerated in the intestines of mice and piglets while reducing the appearance of E. coli. SNIPR001 is now in clinical development and has been granted Fast Track (Urgent Review) designation by the US Food and Drug Administration.
Composed of four complementary CAP processes, SNIPR001 is a novel, selectively targeting micro-antibiotic coli For prevention of bacteremia in leukemia patients at risk of neutropenia (low levels of white blood cells).
Leukemia patients are in the first place
The reason for this exciting new development for leukemia patients has to do with the side effects of chemotherapy. The patient’s bone marrow causes fewer blood cells to be produced and the intestines to become inflamed. The latter increases intestinal permeability allowing bacteria from the gut to travel into the bloodstream. This combination of side effects makes the patient susceptible to infections from bacteria such as coli. In such cases, the
Today, high-risk patients (that is, those with low levels of white blood cells) receive antibiotic treatments before chemotherapy, but in some cases, coli It shows very high resistance to commonly used antibiotics. Also, the antibiotics themselves have many side effects that in some cases reduce the effect of cancer treatments.
“We need to have a variety of options available to treat these patients, preferably ones in which we can specifically target the responsible bacteria to avoid side effects and which do not increase the problem of antibiotic resistance,” says Morten Otto Alexander Sommer.
In recent years, researchers have been looking into using phages to treat infections due to increasing antibiotic resistance. Before antibiotics were widely available, phages were widely used and studied in countries that were then part of the Soviet Union. However, there are few clinical trials, and the results have not been convincing, according to the paper.
“Through emerging technologies such as CRISPR, the use of phages to treat infections is becoming a viable pathway. As our results show, there is potential for enhancing naturally occurring phages through genetic engineering. I hope this approach will also serve as a blueprint for new antimicrobials that target pathogens. resistance,” says Morten Otto Alexander Sommer.
CRISPR treatment, phages and phages
CRISPR technology is a way for scientists to edit the DNA sequence in cells. It is based on a defense mechanism that bacteria naturally use to protect themselves. CRISPR technology uses a molecule called Cas9, which acts like a pair of scissors to cut DNA at a specific location.
After cutting, the DNA can be repaired or a new piece can be added. Scientists can use this tool to create GMOs, find new ways to treat genetic diseases, and learn more about how genes work.
Phages are small viruses that can kill certain bacteria. They are ubiquitous on Earth and help regulate bacterial populations and nutrient cycling. They infect and kill bacteria, and when the bacteria die, they release nutrients into the environment.
Scientists use phages to treat bacterial infections, which is called phage therapy. They identify and isolate phages that can kill a particular bacterial strain and use them to fight infections caused by that strain.
Phage therapy has some advantages over antibiotics, such as targeting specific bacteria without side effects and potentially reducing antibiotic resistance.
background: An overview of the SNIPR001 creation process
- Naturally occurring phages are screened against a panel of coli strains.
- Phages with broad activity against coli are fibers engineered and/or armed with CRISPR-Cas systems that contain sequences specific for coliand the creation of Cas-armed phages.
- These CAPs are tested for host range, in vivo efficacy, and CMC specifications.