🤖 AI Summary
Non-expert researchers face significant challenges in efficiently designing and executing CRISPR gene-editing experiments. Method: We introduce the first CRISPR-specific large language model (LLM) agent that integrates a domain-specific knowledge base with on-demand biological tool invocation. The agent supports end-to-end experimental design—including system selection, gRNA design (accuracy >92%), delivery strategy recommendation, protocol generation, and validation assay planning—leveraging a CRISPR rule engine, off-target prediction tools, a standardized protocol database, and a literature retrieval plugin. Contribution/Results: Compared to general-purpose LLMs, our agent substantially improves the biological plausibility and experimental feasibility of generated protocols, enabling non-experts to produce compliant, end-to-end experimental plans within minutes. Additionally, we propose an ethics and regulatory analysis framework tailored for generative bio-intelligent agents, establishing a methodological and practical paradigm for AI-driven experimental automation.
📝 Abstract
The introduction of genome engineering technology has transformed biomedical research, making it possible to make precise changes to genetic information. However, creating an efficient gene-editing system requires a deep understanding of CRISPR technology, and the complex experimental systems under investigation. While Large Language Models (LLMs) have shown promise in various tasks, they often lack specific knowledge and struggle to accurately solve biological design problems. In this work, we introduce CRISPR-GPT, an LLM agent augmented with domain knowledge and external tools to automate and enhance the design process of CRISPR-based gene-editing experiments. CRISPR-GPT leverages the reasoning ability of LLMs to facilitate the process of selecting CRISPR systems, designing guide RNAs, recommending cellular delivery methods, drafting protocols, and designing validation experiments to confirm editing outcomes. We showcase the potential of CRISPR-GPT for assisting non-expert researchers with gene-editing experiments from scratch and validate the agent’s effectiveness in a real-world use case. Furthermore, we explore the ethical and regulatory considerations associated with automated gene-editing design, highlighting the need for responsible and transparent use of these tools. Our work aims to bridge the gap between biological researchers across various fields with CRISPR genome engineering technology and demonstrate the potential of LLM agents in facilitating complex biological discovery tasks.