How aggressive a tumor is or how well a cancer patient reacts to a particular medication can be greatly impacted by a change in only one letter in the coding that makes up a cancer-causing gene. Instead of being constrained to more broadly focused strategies, such as deleting the entire gene, scientists will be able to analyze the impact of these exact genetic modifications in preclinical models thanks to a new, extremely precise gene editing tool developed by Weill Cornell Medicine investigators.
The gene editing tool was described in a study published Aug. 10 in Nature Biotechnology. Senior author Dr. Lukas Dow, an associate professor of biochemistry in medicine at Weill Cornell Medicine, and his colleagues genetically engineered mice to carry an enzyme that allows the scientists to change a single base or “letter” in the mouse’s genetic code. The enzyme can be turned on or off by feeding the mice an antibiotic called doxycycline, reducing the prospect of unintended genetic changes occurring over time. Investigators can also grow miniature versions of intestine, lung, and pancreas tissue called organoids from the mice enabling even more molecular and biochemical studies of the impact of these precise genetic changes.
“We are excited about using this technology to try and understand the genetic changes that influence a patient’s response to cancer therapies,” said Dr. Dow, who is also a member of the Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine.
Dr. Dow pointed out that variations in a gene’s single base can have functional repercussions. But the majority of the currently accessible gene editing tools target bigger targets, like entire genes. Scientists can also use viruses to transmit genes with particular mutations, although this method is only effective when targeting organs like the liver and brain.
“We’ve had good tools for a long time now to knock genes out or overexpress genes,” Dr. Dow said. “But we have not had good ways to create the single-base mutations that we see in patient’s tumors.”
Using a mouse model, they can examine how the alterations affect tumors and figure out which treatments are most effective for people who have a certain mutation. Organoids made from mice allow for in-depth research in tissues that are difficult for researchers to access using virus-based methods.
“One mouse model allows you to do two things: test the effects of a mutation in cancer initiation, progression, or treatment response in mice and take a closer look at the associated molecular or biochemical changes using organoids,” he said.
In order to determine the impact of single-base mutations in lung, colon, and pancreatic cancer, Dr. Dow and his team—which also includes co-first authors Dr. Alyna Katti, a former graduate student, and Dr. Adrián Vega-Pérez, a postdoctoral associate—are currently utilizing this novel technology. Other researchers will be able to utilize their genetically modified mice, which could hasten the development of a tailored cancer treatment.
“We are making the technology available to other people in the field so they can use it to study their mutations of interest,” Dr. Dow said. “If we can learn the genetic underpinnings of what causes tumor formation and why patients have different outcomes, that may help us develop new drugs or select the best drugs for a particular patient.”
more recommended stories
-
Limited Prenatal COVID-19 Impact on Child Development
In a recent study published in.
-
MethylGPT Unlocks DNA Secrets – Age & Disease Prediction
Researchers recently created a transformer-based foundation.
-
Yellow Fever Vaccine: No Booster Needed, Study Finds
In a recent study published in.
-
Heat Exposure Risks for Maternal & Newborn Health
Extreme heat poses serious health risks.
-
New SCLC Biomarkers Fuel Precision Medicine Advances
On October 11, 2024, a new.
-
Epigenetic Target Boosts Pancreatic Cancer Therapy
A new discovery in pancreatic cancer.
-
Sleep Patterns Linked to Healthy Aging Outcomes
A recent study published in the.
-
AI ECG Model Predicts Heart Disease with Precision
In a recent study published in.
-
Breast Cancer Risk Increase Linked to 80 Genes
Breast cancer is the most frequent.
-
Liquid Biopsy Enhances Cancer Detection
A study team from the University.
Leave a Comment