Di Yin

All Publications

• Dendritic-cell-targeting virus-like particles as potent mRNA vaccine carriers. Nature biomedical engineering Yin, D., Zhong, Y., Ling, S., Lu, S., Wang, X., Jiang, Z., Wang, J., Dai, Y., Tian, X., Huang, Q., Wang, X., Chen, J., Li, Z., Li, Y., Xu, Z., Jiang, H., Wu, Y., Shi, Y., Wang, Q., Xu, J., Hong, W., Xue, H., Yang, H., Zhang, Y., Da, L., Han, Z. G., Tao, S. C., Dong, R., Ying, T., Hong, J., Cai, Y. 2024

  Abstract

  Messenger RNA vaccines lack specificity for dendritic cells (DCs)-the most effective cells at antigen presentation. Here we report the design and performance of a DC-targeting virus-like particle pseudotyped with an engineered Sindbis-virus glycoprotein that recognizes a surface protein on DCs, and packaging mRNA encoding for the Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or for the glycoproteins B and D of herpes simplex virus 1. Injection of the DC-targeting SARS-CoV-2 mRNA vaccine in the footpad of mice led to substantially higher and durable antigen-specific immunoglobulin-G titres and cellular immune responses than untargeted virus-like particles and lipid-nanoparticle formulations. The vaccines also protected the mice from infection with SARS-CoV-2 or with herpes simplex virus 1. Virus-like particles with preferential uptake by DCs may facilitate the development of potent prophylactic and therapeutic vaccines.

  View details for DOI 10.1038/s41551-024-01208-4

  View details for PubMedID 38714892

  View details for PubMedCentralID 7655734

• In Vivo CRISPR Gene Editing in Patients with Herpes Stromal Keratitis. Molecular therapy : the journal of the American Society of Gene Therapy Wei, A., Yin, D., Zhai, Z., Ling, S., Le, H., Tian, L., Xu, J., Paludan, S. R., Cai, Y., Hong, J. 2023

  Abstract

  In vivo CRISPR gene therapy holds large clinical potential, but the safety and efficacy remain largely unknown. Here, we injected a single dose of HSV-1-targeting CRISPR formulation in the cornea of three patients with severe refractory herpes stromal keratitis (HSK) during corneal transplantation. Our study is an investigated initiated, open-label, single-arm, non-randomized interventional trial at a single center (NCT04560790). We found neither detectable CRISPR-induced off-target cleavages by GUIDE-seq nor systemic adverse events for 18 months on average in all three patients. The HSV-1 remained undetectable during the study. Our preliminary clinical results suggest that in vivo gene editing targeting the HSV-1 genome holds acceptable safety as a potential therapy for HSK.

  View details for DOI 10.1016/j.ymthe.2023.08.021

  View details for PubMedID 37658603

• Targeting herpes simplex virus with CRISPR-Cas9 cures herpetic stromal keratitis in mice NATURE BIOTECHNOLOGY Yin, D., Ling, S., Wang, D., Dai, Y., Jiang, H., Zhou, X., Paludan, S. R., Hong, J., Cai, Y. 2021; 39 (5): 567-577

  Abstract

  Herpes simplex virus type 1 (HSV-1) is a leading cause of infectious blindness. Current treatments for HSV-1 do not eliminate the virus from the site of infection or latent reservoirs in the trigeminal ganglia. Here, we target HSV-1 genomes directly using mRNA-carrying lentiviral particles that simultaneously deliver SpCas9 mRNA and viral-gene-targeting guide RNAs (designated HSV-1-erasing lentiviral particles, termed HELP). We show that HELP efficiently blocks HSV-1 replication and the occurrence of herpetic stromal keratitis (HSK) in three different infection models. HELP was capable of eliminating the viral reservoir via retrograde transport from corneas to trigeminal ganglia. Additionally, HELP inhibited viral replication in human-derived corneas without causing off-target effects, as determined by whole-genome sequencing. These results support the potential clinical utility of HELP for treating refractory HSK.

  View details for DOI 10.1038/s41587-020-00781-8

  View details for Web of Science ID 000607034800003

  View details for PubMedID 33432198

  View details for PubMedCentralID PMC7611178

• CRISPR-GPT for agentic automation of gene-editing experiments. Nature biomedical engineering Qu, Y., Huang, K., Yin, M., Zhan, K., Liu, D., Yin, D., Cousins, H. C., Johnson, W. A., Wang, X., Shah, M., Altman, R. B., Zhou, D., Wang, M., Cong, L. 2025

  Abstract

  Performing effective gene-editing experiments requires a deep understanding of both the CRISPR technology and the biological system involved. Meanwhile, despite their versatility and promise, large language models (LLMs) often lack domain-specific knowledge and struggle to accurately solve biological design problems. We present CRISPR-GPT, an LLM agent system to automate and enhance CRISPR-based gene-editing design and data analysis. CRISPR-GPT leverages the reasoning capabilities of LLMs for complex task decomposition, decision-making and interactive human-artificial intelligence (AI) collaboration. This system incorporates domain expertise, retrieval techniques, external tools and a specialized LLM fine tuned with open-forum discussions among scientists. CRISPR-GPT assists users in selecting CRISPR systems, experiment planning, designing guide RNAs, choosing delivery methods, drafting protocols, designing assays and analysing data. We showcase the potential of CRISPR-GPT by knocking out four genes with CRISPR-Cas12a in a human lung adenocarcinoma cell line and epigenetically activating two genes using CRISPR-dCas9 in a human melanoma cell line. CRISPR-GPT enables fully AI-guided gene-editing experiment design and analysis across different modalities, validating its effectiveness as an AI co-pilot in genome engineering.

  View details for DOI 10.1038/s41551-025-01463-z

  View details for PubMedID 40738974

  View details for PubMedCentralID 10876664

• Biomni: A General-Purpose Biomedical AI Agent. bioRxiv : the preprint server for biology Huang, K., Zhang, S., Wang, H., Qu, Y., Lu, Y., Roohani, Y., Li, R., Qiu, L., Li, G., Zhang, J., Yin, D., Marwaha, S., Carter, J. N., Zhou, X., Wheeler, M., Bernstein, J. A., Wang, M., He, P., Zhou, J., Snyder, M., Cong, L., Regev, A., Leskovec, J. 2025

  Abstract

  Biomedical research underpins progress in our understanding of human health and disease, drug discovery, and clinical care. However, with the growth of complex lab experiments, large datasets, many analytical tools, and expansive literature, biomedical research is increasingly constrained by repetitive and fragmented workflows that slow discovery and limit innovation, underscoring the need for a fundamentally new way to scale scientific expertise. Here, we introduce Biomni, a general-purpose biomedical AI agent designed to autonomously execute a wide spectrum of research tasks across diverse biomedical subfields. To systematically map the biomedical action space, Biomni first employs an action discovery agent to create the first unified agentic environment - mining essential tools, databases, and protocols from tens of thousands of publications across 25 biomedical domains. Built on this foundation, Biomni features a generalist agentic architecture that integrates large language model (LLM) reasoning with retrieval-augmented planning and code-based execution, enabling it to dynamically compose and carry out complex biomedical workflows - entirely without relying on predefined templates or rigid task flows. Systematic benchmarking demonstrates that Biomni achieves strong generalization across heterogeneous biomedical tasks - including causal gene prioritization, drug repurposing, rare disease diagnosis, microbiome analysis, and molecular cloning - without any task-specific prompt tuning. Real-world case studies further showcase Biomni's ability to interpret complex, multi-modal biomedical datasets and autonomously generate experimentally testable protocols. Biomni envisions a future where virtual AI biologists operate alongside and augment human scientists to dramatically enhance research productivity, clinical insight, and healthcare. Biomni is ready to use at https://biomni.stanford.edu, and we invite scientists to explore its capabilities, stress-test its limits, and co-create the next era of biomedical discoveries.

  View details for DOI 10.1101/2025.05.30.656746

  View details for PubMedID 40501924

  View details for PubMedCentralID PMC12157518

• Systematic Discovery, In Vivo Delivery, and DNA Repair Mechanism of Single-Strand Annealing Protein for Precision Integration of Large DNA Sequences Cong, L., Yin, D., Xu, G., Qu, Y., Wang, C., Wang, X., Johnson, W., Filsinger, G., Wannier, T., Church, G. M., Phoon, L., Gao, B., Lan, L. CELL PRESS. 2024: 9-10

  View details for Web of Science ID 001332783400018

• Long sequence insertion via CRISPR/Cas gene-editing with transposase, recombinase, and integrase. Current opinion in biomedical engineering Wang, X., Xu, G., Johnson, W. A., Qu, Y., Yin, D., Ramkissoon, N., Xiang, H., Cong, L. 2023; 28

  Abstract

  CRISPR/Cas-based gene-editing technologies have emerged as one of the most transformative tools in genome science over the past decade, providing unprecedented possibilities for both fundamental and translational research. Following the initial wave of innovations for gene knock-out, epigenetic/RNA modulation, and nickase-mediated base-editing, recent efforts have pivoted towards long-sequence gene editing- specifically, the insertion of large fragments (>1 kb) into the endogenous genome. In this review, we survey the development of these CRISPR/Cas-based sequence insertion methodologies in conjunction with the emergence of novel families of editing enzymes, such as transposases, single-stranded DNA-annealing proteins, recombinases, and integrases. Despite facing a number of challenges, this field continues to evolve rapidly and holds the potential to catalyze a new wave of revolutionary biomedical applications.

  View details for DOI 10.1016/j.cobme.2023.100491

  View details for PubMedID 38549686

  View details for PubMedCentralID PMC10976843

• Long sequence insertion via CRISPR/Cas gene-editing with transposase, recombinase, and integrase CURRENT OPINION IN BIOMEDICAL ENGINEERING Wang, X., Xu, G., Johnson, W. A., Qu, Y., Yin, D., Ramkissoon, N., Xiang, H., Cong, L. 2023; 28

  View details for DOI 10.1016/j.cobme.2023.100491

  View details for Web of Science ID 001062222100001

• A supramolecular gel with unique rheological properties for treating corneal virus infection NANO TODAY Hu, J., Zhou, X., Chen, S., Yin, D., Yang, Y., Chen, M., Gui, C., Cai, Y., Hong, J., Cheng, Y. 2023; 50

  View details for DOI 10.1016/j.nantod.2023.101841

  View details for Web of Science ID 000981002200001

• The Inactivated gE/TK Gene-Deleted Vaccine Against Pseudorabies Virus Type II Confers Effective Protection in Mice and Pigs FRONTIERS IN MICROBIOLOGY Jin, Y., Yin, D., Xing, G., Huang, Y., Fan, C., Fan, C., Qiu, X., Dong, W., Yan, Y., Gu, J., Zhou, J. 2022; 13: 943707

  Abstract

  The highly virulent and antigenic variant of Pseudorabies virus (PRV) that emerged from classical Bartha-K61-vaccinated pig herds has caused substantial economic losses to the swine industry in China since 2011. A safe and more effective vaccine is most desirable. In this study, a gE/TK gene-deficient PRV, namely, HD/c, was constructed based on a PRV type II DX strain isolated from a commercial vaccine-immunized farm and the HD/c-based inactivated vaccine was formulated and evaluated for its safety, immunogenicity, and protective efficacy in mice and piglets. The resulting PRV HD/c strain has a similar growth curve to the parental DX strain. After vaccination, the inactivated HD/c vaccine did not cause any visible gross pathological or histopathological changes in the tissues of mice and piglets and provided rapid and potent protection against the challenge of the classical and variant PRVs at day 21 post-vaccination in mice. A single immunization of 108.5TCID50 inactivated PRV HD/c strain-elicited robust immunity with high titer of neutralizing antibody and provided complete protection from the lethal challenge of PRV DX strain in piglets. These results indicated that the inactivated PRV HD/c vaccine with the deletion of gE/TK genes was a safe and effective PRV vaccine candidate for the control of PRV.

  View details for DOI 10.3389/fmicb.2022.943707

  View details for Web of Science ID 000843079600001

  View details for PubMedID 35992698

  View details for PubMedCentralID PMC9389536

• Lentiviral delivery of co-packaged Cas9 mRNA and a Vegfa-targeting guide RNA prevents wet age-related macular degeneration in mice NATURE BIOMEDICAL ENGINEERING Ling, S., Yang, S., Hu, X., Yin, D., Dai, Y., Qian, X., Wang, D., Pan, X., Hong, J., Sun, X., Yang, H., Paludan, S., Cai, Y. 2021; 5 (2): 144-156

  Abstract

  Therapeutic genome editing requires effective and targeted delivery methods. The delivery of Cas9 mRNA using adeno-associated viruses has led to potent in vivo therapeutic efficacy, but can cause sustained Cas9 expression, anti-Cas9 immune responses and off-target edits. Lentiviral vectors have been engineered to deliver nucleases that are expressed transiently, but in vivo evidence of their biomedical efficacy is lacking. Here, we show that the lentiviral codelivery of Streptococcus pyogenes Cas9 mRNA and expression cassettes that encode a guide RNA that targets vascular endothelial growth factor A (Vegfa) is efficacious in a mouse model of wet age-related macular degeneration induced by Vegfa. A single subretinal injection of engineered lentiviruses knocked out 44% of Vegfa in retinal pigment epithelium and reduced the area of choroidal neovascularization by 63% without inducing off-target edits or anti-Cas9 immune responses. Engineered lentiviruses for the transient expression of nucleases may form the basis of new treatments for retinal neovascular diseases.

  View details for DOI 10.1038/s41551-020-00656-y

  View details for Web of Science ID 000604859600002

  View details for PubMedID 33398131

  View details for PubMedCentralID 5898607