OpenCRISPR-1: The Science Behind AI-Designed Gene Editing

AI-Enhanced Genome Editing: What’s New

Our latest clinical gene editing offerings combine REPROCELL’s StemRNA™ Clinical iPSC Seed Clones with OpenCRISPR-1™, an AI-designed genome editing system licensed from Profluent Bio (Emeryville, CA, USA) to enable streamlined engineering workflows and ensure a GMP-aligned, traceable, and regulatory-ready platform from the outset.

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Reduced off-target edits for safer clinical gene modification

Advantages of StemEdit Clinical Gene Editing Over Other Caspases

✓Broader targeting scope

✓Improved safety & specificity

✓Can be used with existing Cas9 guides or with customized “designer” editors

✓Platform scalability & democratization

✓Accelerated therapeutic development

How OpenCRISPR-1 Works

AI Meets Gene Editing

OpenCRISPR-1’s design begins with large protein language models (LLMs) pre-trained on millions of naturally occurring CRISPR–Cas sequences to learn the underlying principles of functional genome editors. These models are then fine-tuned specifically on CRISPR–Cas data to guide generation toward proteins with the structural and functional characteristics of Cas9-like nucleases, creating novel gene editors far outside the range of sequences found in nature. From millions of AI-generated candidates, OpenCRISPR-1 was identified for its strong editing activity, on-target efficiency comparable to traditional SpCas9, and reduced off-target effects in human cells, addressing key challenges in precision editing for clinical use. The system also supports fusion with base-editing domains to enable single-base conversions without double-strand breaks, thereby broadening its applicability for therapeutic workflows (Ruffolo et al., 2025).

Figure 1. AI-driven design of OpenCRISPR-1. Large language models (LLMs) are first pretrained on a diverse, evolution-wide set of protein sequences - enabling them to learn general constraints of protein evolution and then fine-tuned with CRISPR/Cas (nuclease + nucleic acid) data to generate novel, functional Cas-like proteins such as OpenCRISPR-1.

Figure 2. Mechanism of CRISPR-guided DNA targeting. In CRISPR-based editing systems like OpenCRISPR-1, a guide RNA directs the editor protein to a specific DNA sequence, where catalytic domains introduce precise edits. OpenCRISPR-1’s AI-designed architecture maintains this core mechanism while enhancing on-target specificity and reducing off-target activity

REPROCELL & Profluent Bio

Combining AI Protein Design with Clinical Gene Editing Expertise

OpenCRISPR-1 is licensed from Profluent Bio, combining REPROCELL’s clinical gene editing infrastructure with Profluent’s AI-driven protein design capabilities (editor generation and optimization).

See press release, REPROCELL Launches StemEdit: Clinical Gene Editing Services and New iPSC Lines Using AI-Designed Editing System

References

1. Evangelou C. OpenCRISPR-1: Generative AI Meets CRISPR. CRISPR Medicine News (2024).
2. Ruffolo JA, Nayfach S, Gallagher J, et al. Design of highly functional genome editors by modelling CRISPR-Cas sequences. Nature 645(8080):518-525, (2025).
3. Thomson T, Li G, Strilchuk A, et al. Harnessing artificial intelligence to advance CRISPR-based genome editing technologies. Nature Reviews Genetics 27, pages 212–230, (2026).