AI Boosts Gene Therapy Speed

Stanford Medicine researchers have developed an artificial intelligence tool to help scientists better plan gene-editing experiments. The technology, CRISPR-GPT, acts as a gene-editing "copilot" supported by AI to help researchers—even those unfamiliar with gene editing—generate designs, analyze data and troubleshoot design flaws.

The model builds on a tool called CRISPR, a powerful gene-editing technology used to edit genomes and develop therapies for genetic diseases. But training on the tool to design an experiment is complicated and time-consuming—even for seasoned scientists. CRISPR-GPT speeds that process along, automating much of the experimental design and refinement. The goal, said Le Cong, Ph.D., assistant professor of pathology and genetics, who led the technology's development, is to help scientists produce lifesaving drugs faster.

The paper is published in the journal Nature Biomedical Engineering.

"The hope is that CRISPR-GPT will help us develop new drugs in months, instead of years," Cong said. "In addition to helping students, trainees and scientists work together, having an AI agent that speeds up experiments could also eventually help save lives."

In addition, it could expand the pool of scientists who can effectively use gene editing technology—no experience required. For instance, a student in Cong's lab used CRISPR-GPT to successfully guide an experiment that turned off a handful of genes in lung cancer cells on his first attempt. That kind of feat usually requires a prolonged period of trial and error. But the AI tool's ability to flatten CRISPR's steep learning curve seems like a promising way to open access to gene editing throughout the biotechnology, agriculture and medical industries, Cong said.

"Trial and error is often the central theme of training in science," Cong said. "But what if it could just be trialed and done?"

Cong is the senior author of the study. The lead authors are Yuanhao Qu, a graduate student in cancer biology, and Kaixuan Huang, a collaborating graduate student at Princeton University.

AI that thinks like a human

CRISPR can target sections of DNA and snip out problematic mutations—the conceptual basis for many genetic disease therapies such as sickle cell anemia. But it can take months of guess-and-check work for researchers to evaluate whether the suspected segment of DNA is indeed the culprit they need to excise. (CRISPR can sometimes accidentally edit the wrong gene sequence, leading to unwanted genetic effects.)

CRISPR-GPT uses years of published data to hone the experimental design into something likely to be successful. It can also predict off-target edits and their likelihood of causing damage, allowing experts to choose the best path forward.

Cong's team trained their model with 11 years' worth of expert discussions, captured online, from CRISPR experiments and information published in scientific papers. The result? An AI model that "thinks" like a scientist.

When using CRISPR-GPT, the researcher initiates a conversation with the AI agent through a text chat box, providing experimental goals, context and relevant gene sequences. Then, CRISPR-GPT creates a plan that suggests experimental approaches and identifies problems that have occurred in similar experiments to help the researcher—novice or expert—avoid them.

Yilong Zhou, a visiting undergraduate student from Tsinghua University, used CRISPR-GPT to successfully activate genes in A375 melanoma cancer cells as part of his research into better understanding why cancer immunotherapy sometimes fails.

Zhou typed his question into CRISPR-GPT's text box: "I plan to do a CRISPR activate in a culture of human lung cells, what method should I use?"

CRISPR-GPT responded like an experienced lab mate advising a new researcher. It drafted an experimental design, and at each step, explained its "thought" process, describing why the various steps were important.

"I could simply ask questions when I didn't understand something, and it would explain or adjust the design to help me understand," Zhou said. "Using CRISPR-GPT felt less like a tool and more like an ever-available lab partner."

As an early-career scientist, Zhou had designed only a handful of CRISPR experiments prior to using CRISPR-GPT. In this experiment, it took him one attempt to get it right—a rarity for most scientists.

In the past, Zhou was constantly worrying about making mistakes and double-checking his designs.

Reducing error and increasing accessibility

CRISPR-GPT can toggle between three modes: beginner, expert and Q&A. The beginner mode functions as a tool and a teacher, providing an answer and explanation for each recommendation. Expert mode is more of an equal partner, working with advanced scientists to tackle complex problems without providing additional context. Any researcher can use the Q&A function to directly address specific questions.