# CRISPR-GPT for Agentic Automation of Gene-editing Experiments

arXiv: https://arxiv.org/abs/2404.18021 · HTML: https://mlsanity.com/paper/2404.18021/

## Key facts

- Cited by 58 papers in the map (data through 14 Oct 2026).
- Placed in Medical and scientific domain agents, one of 16 directions in LLM agents and tool use.
- Builds on 22 of its 91 references that are in the map.
- First posted on arXiv 27 Apr 2024.

## Placed in

- LLM agents and tool use / [Medical and scientific domain agents](https://mlsanity.com/agents/medical-and-scientific-domain-agents/)

## Builds on (most cited first, 22 of 22)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
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- [RoBERTa: A Robustly Optimized BERT Pretraining Approach](https://mlsanity.com/paper/1907.11692/) (2019)
- [Chain-of-Thought Prompting Elicits Reasoning in Large Language Models](https://mlsanity.com/paper/2201.11903/) (2022)
- [ReAct: Synergizing Reasoning and Acting in Language Models](https://mlsanity.com/paper/2210.03629/) (2022)
- [PaLM: Scaling Language Modeling with Pathways](https://mlsanity.com/paper/2204.02311/) (2022)
- [Toolformer: Language Models Can Teach Themselves to Use Tools](https://mlsanity.com/paper/2302.04761/) (2023)
- [QLoRA: Efficient Finetuning of Quantized LLMs](https://mlsanity.com/paper/2305.14314/) (2023)
- [Training Compute-Optimal Large Language Models](https://mlsanity.com/paper/2203.15556/) (2022)
- [Voyager: An Open-Ended Embodied Agent with Large Language Models](https://mlsanity.com/paper/2305.16291/) (2023)
- [Least-to-Most Prompting Enables Complex Reasoning in Large Language Models](https://mlsanity.com/paper/2205.10625/) (2022)
- [Gorilla: Large Language Model Connected with Massive APIs](https://mlsanity.com/paper/2305.15334/) (2023)
- [HuggingGPT: Solving AI Tasks with ChatGPT and its Friends in Hugging Face](https://mlsanity.com/paper/2303.17580/) (2023)
- [PaLM 2 Technical Report](https://mlsanity.com/paper/2305.10403/) (2023)
- [BloombergGPT: A Large Language Model for Finance](https://mlsanity.com/paper/2303.17564/) (2023)
- [Large Language Models as Optimizers](https://mlsanity.com/paper/2309.03409/) (2023)
- [ChemCrow: Augmenting large-language models with chemistry tools](https://mlsanity.com/paper/2304.05376/) (2023)
- [Large Language Models as Tool Makers](https://mlsanity.com/paper/2305.17126/) (2023)
- [ToolkenGPT: Augmenting Frozen Language Models with Massive Tools via Tool Embeddings](https://mlsanity.com/paper/2305.11554/) (2023)
- [Chain-of-Table: Evolving Tables in the Reasoning Chain for Table Understanding](https://mlsanity.com/paper/2401.04398/) (2024)
- [Mind's Eye: Grounded Language Model Reasoning through Simulation](https://mlsanity.com/paper/2210.05359/) (2022)
- [BioPlanner: Automatic Evaluation of LLMs on Protocol Planning in Biology](https://mlsanity.com/paper/2310.10632/) (2023)

## Built on by (most cited first, 30 of 58)

- [A Review of Large Language Models and Autonomous Agents in Chemistry](https://mlsanity.com/paper/2407.01603/) (2024)
- [A Comprehensive Survey of Scientific Large Language Models and Their Applications in Scientific Discovery](https://mlsanity.com/paper/2406.10833/) (2024)
- [Agentic AI for Scientific Discovery: A Survey of Progress, Challenges, and Future Directions](https://mlsanity.com/paper/2503.08979/) (2025)
- [From AI for Science to Agentic Science: A Survey on Autonomous Scientific Discovery](https://mlsanity.com/paper/2508.14111/) (2025)
- [Many Heads Are Better Than One: Improved Scientific Idea Generation by A LLM-Based Multi-Agent System](https://mlsanity.com/paper/2410.09403/) (2024)
- [BioDiscoveryAgent: An AI Agent for Designing Genetic Perturbation Experiments](https://mlsanity.com/paper/2405.17631/) (2024)
- [A Survey of Agentic Reasoning for Large Language Models: Towards Recursively Self-Improving and Collective Agents](https://mlsanity.com/paper/2601.12538/) (2026)
- [Towards Scientific Discovery with Generative AI: Progress, Opportunities, and Challenges](https://mlsanity.com/paper/2412.11427/) (2024)
- [SKILLFOUNDRY: Building Self-Evolving Agent Skill Libraries from Heterogeneous Scientific Resources](https://mlsanity.com/paper/2604.03964/) (2026)
- [Virology Capabilities Test (VCT): A Multimodal Virology Q&A Benchmark](https://mlsanity.com/paper/2504.16137/) (2025)
- [Aviary: training language agents on challenging scientific tasks](https://mlsanity.com/paper/2412.21154/) (2024)
- [Paper2Agent: Reimagining Research Papers As Interactive and Reliable AI Agents](https://mlsanity.com/paper/2509.06917/) (2025)
- [Agentic AI Needs a Systems Theory](https://mlsanity.com/paper/2503.00237/) (2025)
- [AnalogXpert: Automating Analog Topology Synthesis by Incorporating Circuit Design Expertise into Large Language Models](https://mlsanity.com/paper/2412.19824/) (2024)
- [OmniScientist: Toward a Co-evolving Ecosystem of Human and AI Scientists](https://mlsanity.com/paper/2511.16931/) (2025)
- [E-valuator: Reliable Agent Verifiers with Sequential Hypothesis Testing](https://mlsanity.com/paper/2512.03109/) (2025)
- [ChemToolAgent: The Impact of Tools on Language Agents for Chemistry Problem Solving](https://mlsanity.com/paper/2411.07228/) (2024)
- [Autonomous Agents for Scientific Discovery: Orchestrating Scientists, Language, Code, and Physics](https://mlsanity.com/paper/2510.09901/) (2025)
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- [Contextualizing biological perturbation experiments through language](https://mlsanity.com/paper/2502.21290/) (2025)
- [Toward Greater Autonomy in Materials Discovery Agents: Unifying Planning, Physics, and Scientists](https://mlsanity.com/paper/2506.05616/) (2025)
- [Pathology-CoT: Learning Visual Chain-of-Thought Agent from Expert Whole Slide Image Diagnosis Behavior](https://mlsanity.com/paper/2510.04587/) (2025)
- [LLMs Outperform Experts on Challenging Biology Benchmarks](https://mlsanity.com/paper/2505.06108/) (2025)
- [Autonomous Research Agents: A Survey of AI Scientists and the Verification Gap](https://mlsanity.com/paper/2608.05179/) (2026)
- [MetaScientist: A Human-AI Synergistic Framework for Automated Mechanical Metamaterial Design](https://mlsanity.com/paper/2412.16270/) (2024)
- [Adapting While Learning: Grounding LLMs for Scientific Problems with Intelligent Tool Usage Adaptation](https://mlsanity.com/paper/2411.00412/) (2024)
- [From Intention To Implementation: Automating Biomedical Research via LLMs](https://mlsanity.com/paper/2412.09429/) (2024)
- [Advancing the Scientific Method with Large Language Models: From Hypothesis to Discovery](https://mlsanity.com/paper/2505.16477/) (2025)
- [Toward Scientific Reasoning in LLMs: Training from Expert Discussions via Reinforcement Learning](https://mlsanity.com/paper/2505.19501/) (2025)
- [BioMARS: A Multi-Agent Robotic System for Autonomous Biological Experiments](https://mlsanity.com/paper/2507.01485/) (2025)

## Abstract (arXiv)

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 beginner biological researchers and CRISPR genome engineering techniques, and demonstrate the potential of LLM agents in facilitating complex biological discovery tasks. The published version of this draft is available at https://www.nature.com/articles/s41551-025-01463-z.