Ruijie Fu, Jingwei Hong, Qiang Qu, Zhiling Hong, Qingshan Jiang, Yunlei Xianyu
Storing magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging data in DNA offers a promising solution for the long-term archival management of rapidly expanding biomedical image volumes. However, querying these data typically requires polymerase chain reaction and sequencing, which increases readout complexity and retrieval latency. Here, we propose a CRISPR-Cas12a-based querying strategy that leverages the programmability of CRISPR RNA (crRNA) for precise matching with identifier (ID) sequences. In this approach, crRNA functions as a query tool that identifies matching IDs and triggers detectable signals. Through a one-to-one mapping between ID and payload sequences established during encoding, the corresponding image data can be retrieved upon query. Computational simulations demonstrate over 99% query accuracy for both MRI and PET data using crRNA. CRISPR-Cas12a cleavage assays and molecular docking further validate the high specificity of crRNA-ID recognition. This work demonstrates the potential of CRISPR-Cas12a for biochemical querying of DNA-encoded biomedical imaging data, enabling targeted access to indexed sequences.