OpenCrisper-1

Extracted Attributes

• CEO Quote

  Attempting to edit human DNA with an AI-designed biological system was a scientific moonshot. Our success points to a future where AI precisely designs what is needed to create a range of bespoke cures for disease. - Ali Madani, Profluent cofounder and CEO

• Developer

  Profluent Bio

• Components

  Cas9-like protein and guide RNA

• Specificity

  Higher than SpCas9

• Architecture

  Maintains prototypical architecture of a Type II Cas9 nuclease

• AI Model Used

  Protein language model (analogous to LLMs)

• PAM Preference

  NGG PAM

• Creation Method

  AI-created, fully synthetic genome editor

• Technology Type

  Gene editing tool

• Open-source Status

  Freely available to license for ethical research and commercial uses

• Location of Developer

  Berkeley, California, United States

• Distinguishing Feature

  Hundreds of mutations away from SpCas9 (>400 mutations) and other natural CRISPR-associated proteins (~180-200 mutations)

• Off-target Edits Reduction

  95% compared to SpCas9

• On-target Editing Efficiency

  Comparable to SpCas9

Timeline

• OpenCRISPR-1 officially released as an AI-designed, RNA-programmable gene editor with NGG PAM preference. (Source: Web Search Results)

  2024-04-22

• Profluent successfully edits the human genome with OpenCRISPR-1, demonstrating the first successful precision editing of human DNA with customizable gene editors designed from scratch with AI. (Source: Web Search Results)

  2024-04-22

• Work on OpenCRISPR-1, including its generation and characterization, is described in a publication by Ruffolo, Nayfach, Gallagher, and Bhatnagar et al. in Nature magazine. (Source: Web Search Results)

  2025-XX-XX

Cosmic Crisp

Cosmic Crisp is an American apple with the cultivar designation WA 38, a cross between Honeycrisp and Enterprise apples. Breeding began in 1997 at Washington State University, and the apple was commercially released in 2019. The Cosmic Crisp has seen strong and growing sales since its launch. As of 2025, it was the sixth most-produced apple variety grown in the United States.

Web Search Results

• Profluent-AI/OpenCRISPR: AI-generated gene editing systems

  What is OpenCRISPR-1? OpenCRISPR-1 is an AI-created gene editor, consisting of a Cas9-like protein and guide RNA, fully developed using Profluent’s large language models (LLMs). The OpenCRISPR-1 protein maintains the prototypical architecture of a Type II Cas9 nuclease but is hundreds of mutations away from SpCas9 or any other known natural CRISPR-associated protein. You can view OpenCRISPR-1 as a drop-in replacement for many protocols that need a cas9-like protein with an NGG PAM and you can [...] even use it with canonical SpCas9 gRNAs. OpenCRISPR-1 can be fused in a deactivated or nickase format for next generation gene editing techniques like base, prime, or epigenome editing. Find out more in our preprint. [...] | Release | Date | Description | --- | OpenCRISPR-1 | 2024-04-22 | AI-designed, RNA-programmable gene editor with NGG PAM preference. Described in Ruffolo, Nayfach, Gallagher, and Bhatnagar et al., Nature (2025). | ## FAQs

• Profluent Successfully Edits Human Genome with OpenCRISPR-1 ...

  OpenCRISPR-1 is an AI-created gene editor, consisting of a Cas9-like protein and guide RNA, fully developed using Profluent’s large language models (LLMs). Through the training process for OpenCRISPR, the company’s AI learned from massive scale sequence and biological context to generate millions of diverse CRISPR-like proteins that do not occur in nature, thereby exponentially expanding virtually all known CRISPR families. [...] In its commitment to democratizing the technology, Profluent has launched OpenCRISPR-1 as an initial open-source release, making the AI-designed gene editor freely available to license for ethical research and commercial uses. [...] # Profluent Successfully Edits Human Genome with OpenCRISPR-1, the World’s First AI-Created and Open-Source Gene Editor From the press release. Profluent, the AI-first protein design company, today debuted the OpenCRISPRTM initiative, releasing the world’s first open-source, AI-generated gene editor. With this launch, Profluent demonstrates the first successful precision editing of the human genome with customizable gene editors designed from scratch with AI.

• Profluent Modalities | Gene Editing

  #### OpenCRISPR-1 is an AI-created gene editor, consisting of a Cas9-like protein and guide RNA, fully developed using Profluent’s large language models (LLMs). The OpenCRISPR-1 protein maintains the prototypical architecture of a Type II Cas9 nuclease but is hundreds of mutations away from SpCas9 or any other known natural CRISPR-associated protein. You can view OpenCRISPR-1 as a drop-in replacement for many protocols that need a Cas9-like protein with an NGG PAM and you can even use it with [...] We have decided to launch OpenCRISPR-1 (one of our AI-created gene editors) as an initial open-source release, making it freely available to license for ethical research and commercial uses. OpenCRISPR-1 maintains the prototypical architecture of a Type II Cas9 nuclease but is >400 mutations away from SpCas9 and nearly 200 mutations away from any other known natural CRISPR-associated protein. We also used our LLMs to generate a synthetic guide RNA that could be assembled with OpenCRISPR-1. [...] In our recently released manuscript, we describe both the generation and characterization of OpenCRISPR-1. When delivered via plasmids in HEK293T cells, OpenCRISPR-1 showed comparable on-target editing efficiency and higher specificity relative to SpCas9, across a wide range of genomic on- and off-targets. Furthermore, when combined with AI-generated deaminases, OpenCRISPR-1 was able to assume functionality of a base editing architecture, showing robust A-to-G editing at a panel of target

• Profluent releases AI-enabled OpenCRISPR-1 to edit the human ...

  After narrowing down the results, they identified OpenCRISPR-1, a protein performing similarly to Cas9 but with far less impact on off-target sites. This makes it more precise and causes minimal damage to DNA. The goal of open-sourcing OpenCRISPR-1 is to encourage the use of AI for ethical research and commercial use, particularly in developing medicines leveraging CRISPR. [...] The company is open-sourcing OpenCRISPR-1 for free ethical research and commercial use and published the science behind the protein's development in a preprint publication. "Attempting to edit human DNA with an AI-designed biological system was a scientific moonshot,” Ali Madani, Profluent cofounder and CEO, said in a statement. "Our success points to a future where AI precisely designs what is needed to create a range of bespoke cures for disease." WHY THIS MATTERS

• Profluent's OpenCRISPR-1 published in Nature magazine

  OpenCRISPR-1 is not merely a new tool. It’s the first fully synthetic genome editor, born not from directed evolution or structural tinkering, but from massive-scale data-driven learning. It reflects a shift in biotech: from bioprospecting to bioengineering, from natural history to generative design. And Profluent has open-sourced it all. [...] Today marks a significant scientific milestone for frontier AI systems in biology. Our portfolio company Profluent has its work on OpenCRISPR-1, the first AI-designed CRISPR-Cas protein that can precisely edit human DNA, published in the highest impact scientific journal, Nature. [...] The model, fine-tuned on Cas-specific sequences, was prompted to generate 350,000 synthetic proteins, which were then filtered for quality and CRISPR compatibility. From these, 209 candidates were tested in human cells. The standout was OpenCRISPR-1, a protein 403 mutations away from SpCas9 and 180 mutations from its nearest natural cousin. Despite this evolutionary sequence difference, it matched SpCas9’s on-target activity while reducing off-target edits by 95%!