Shanghai Jiao Tong University to Transfer Two Core Patents on Ultra-Long DNA Synthesis and Spatial Multi-Omics Chip Technologies to Diying Biotech
Recently, Shanghai Jiao Tong University proposed to transfer its ownership of two core patent technologies to the co-owner, Dynasty Gene (Shanghai Diying Biotechnology Co., Ltd.), through related-party transfers. These two patents are“Spatially Interleaved Encoding-Based Multi-Omics Chip, Its Preparation Method and Application” and “Application of Silica Microspheres in the Synthesis of Ultra-Long Oligonucleotides and Method for Synthesizing Ultra-Long Oligonucleotides”, with patent rights equally shared (50% each) by Shanghai Jiao Tong University and Dynasty Gene, among which the assessed value of chip-related patents is240,000 yuan。
As the dual entities serving as the core of technological R&D and the transferee, Professor Shi Yongyong’s R&D team and Shanghai Dynasty Gene Biotechnology Co., Ltd. jointly constitute the key support for this technology transfer.
Both patented technologies are byShanghai Jiao Tong UniversityProf. Shi Yongyong’s TeamR&D completed. The team has long been deeply engaged in the interdisciplinary fields of biotechnology, micro-nano engineering, and information science, establishing end-to-end R&D capabilities spanning from methodology to chip design in the field of high-throughput synthesis and sequencing technologies. Its core advantage lies in innovative“Spatial Interleaved Coding” Strategy, successfully overcoming the industry bottleneck in traditional multi-omics testing, where throughput, cost, and accuracy are difficult to balance.
Professor Shi Yongyong himself possesses a profound academic background and extensive research experience. He is not onlyRecipient of honors such as the Ministry of Education’s New Century Excellent Talents and Shanghai Young Science and Technology Elite, also serves as the principal investigator for key projects funded by the National Natural Science Foundation of China, and concurrently holds positions as a member of the Young Scientists Committee of the Chinese Society of Genetics, a council member of the Shanghai Society of Genetics, and an editorial board member of the journal Experimental Biology and Medicine. To date, his/her team has publishedOver 100 SCI-indexed papers, total impact factor>1,000Total Citations:Over 2,000 times, with research interests broadly covering genetic studies of human complex traits such as diseases and behaviors, spanning multiple fields including molecular genetics, bioinformatics, nanoscience, and developmental biology.
The assignee of this patent, Dynasty Gene (Shanghai) Biotechnology Co., Ltd., is a key industrial force driving the practical application and commercialization of technology. Established in 2018 and headquartered in Shanghai, the company is one of the few domestic enterprises capable of commercially delivering ultra-high-throughput next-generation DNA synthesis. It has secured hundreds of millions of yuan in investment from prominent institutions such as Volcanic Stone Capital, LifeSci Capital, and ByteDance.
Dynasty GeneFocused on the research and development of next-generation nucleic acid synthesis technologies, it provides core support for fields such as synthetic biology, molecular diagnostic reagents, and biopharmaceutical tools. Its independently developed 3D inkjet printing-based ultra-high-throughput in situ DNA synthesis platform has achieved a breakthrough in China, laying a solid foundation for the industrial application of the two patented technologies.
Two patented technologies developed by Shi Yongyong’s team precisely address core technical bottlenecks in current life sciences research from the dimensions of “high-throughput spatial localization analysis” and “long-chain DNA synthesis,” providing innovative solutions to industry challenges.
Bottleneck 1: The Triple Challenges of Spatial Transcriptomics Technology
In the precise diagnosis and mechanistic studies of complex diseases such as cancer and neurodegenerative disorders, there is an urgent need for scientists to obtain the authentic gene expression profiles of cells within their native tissue environments. Spatial transcriptomics serves as a pivotal tool to achieve this objective; it enables the detection of gene activity at distinct spatial locations while preserving the architectural integrity of tissues. By integrating multiple technologies, including histopathology, microarrays, and high-throughput sequencing, spatial transcriptomics was named the Method of the Year 2020 by *Nature Methods*.
However, current spatial transcriptomics technologies face three core challenges: insufficient spatial resolution, limited gene detection rates, and incomplete tissue coverage. Mainstream technologies and commercial platforms all exhibit significant limitations:
Microdissection-based techniques (e.g., Geo-seq):It can only analyze specific preselected sites within tissues, failing to achieve comprehensive transcriptome coverage and resulting in the loss of extensive regional information;
In situ hybridization/sequencing-based technologies (e.g., seqFISH):Relying on pre-designed gene probe panels allows for the detection of only a limited number of known genes, failing to unbiasedly discover novel gene expression information;
Spatial barcode-based in situ capture techniques (e.g., Slide-seq):Although whole-transcriptome analysis can be performed, the spatial resolution is insufficient to distinguish individual cells, and gaps in the probe array result in detection blind spots in tissue sections;
Even the most commercially successful technologies currently available feature detection spots of 55 μm, which are significantly larger than the 10-μm diameter of human cells. Consequently, they can only achieve regional resolution, and the 45-μm spot spacing results in substantial portions of tissue remaining undetected. While methods combining single-cell sequencing to enhance resolution exist, they are time-consuming, labor-intensive, and costly.
These limitations make it difficult for researchers to comprehensively capture cellular heterogeneity within the tissue microenvironment, creating an urgent need for next-generation technologies that can simultaneously meet the requirements of large-scale analysis, single-cell resolution, and comprehensive coverage.
Bottleneck 2: Technical Constraints in Ultra-Long Oligonucleotide Synthesis
OligonucleotideAs a foundational material for molecular biology research, it is widely used in fields such as PCR, gene editing, DNA sequencing, and gene therapy. With technological advancements, scientific research has placed higher demands on the length and quality of oligonucleotides; however, current synthesis methods are approaching a plateau and face numerous challenges:
On one hand, the deprotecting agents, coupling reagents, and nucleotide monomers used in the synthesis process are prone to triggering side reactions such as depurination and incomplete capping, making the synthesis of ultra-long oligonucleotides extremely challenging. On the other hand, even when employing a “fragment ligation” strategy to extend oligonucleotide length, efficacy remains limited when dealing with complex sequences (such as those with DNA secondary structures, repetitive sequences, or extreme GC content). The preparation of ultra-long single-stranded DNA remains a significant industry bottleneck, urgently requiring breakthroughs in novel synthesis processes to overcome these limitations.
To address the aforementioned two major technical bottlenecks, the two patented technologies developed by Shi Yongyong’s team have provided targeted solutions, forming“A Technical Closed Loop of ‘Analytical Tools + Synthetic Foundations’.”
Option 1: Spatially Interleaved Encoded Multi-Omics Chip—Reconstructing Spatial Transcriptomics Analysis Capabilities
Addressing the pain points of existing spatial transcriptomics technologies, the team has proposed a multi-omics chip based on a spatial interleaved encoding strategy. By integrating 3D inkjet in situ DNA synthesis technology, this approach achieves an integrated breakthrough in single-cell resolution, large-scale coverage, and high-throughput multi-omics analysis. Its core innovations are concentrated in three aspects:
1. Unique Spatial Interleaved Encoding Design:Breaking away from the traditional chip rule of XY lattice arrangement, the intersection parts of adjacent circular dots are divided into Zone 2 (intersection of two circles) and Zone 3 (intersection of three circles), while the independent part is designated as Zone 1. Through mathematical model optimization, when the ratio of the center-to-center distance to the radius is approximately 1.285, the areas of the three zones are most similar, achieving uniform resolution. Meanwhile, spatial coordinate barcodes of different lengths are assigned to different zones (Zone 1 has a length of n, Zone 2 has 2n, and Zone 3 has 3n, where n represents the number of bases), greatly enriching the spatial information capacity. Precise positioning at the single-cell level can be achieved through sequencing and decoding.
2. Efficient Preparation Process:By employing high-throughput in situ inkjet printing synthesis technology, this method involves substrate surface treatment (using Piranha solution and plasma cleaning, as well as hydrophilic-hydrophobic silane mixed treatment), the introduction of Spacer reagents (to extend synthesis arms and reduce steric hindrance) and UnyLinker molecules (to link nucleotides), followed by stepwise deposition of nucleotides via a piezoelectric inkjet printhead using a nested strategy of “odd-numbered columns first, then even-numbered columns,” thereby ensuring that the spatial coordinate barcode for each spot is unique and accurate.
3. Diversified Application Expansion Capabilities:The chip-based probes contain universal sequences, spatial coordinate barcodes, molecular tags, and bridging sequences. In transcriptome analysis, they capture mRNA and convert it into sequencing libraries through hybridization, polymerase extension, and ligation reactions. Furthermore, by modifying the probe design, the platform can be extended to epigenomic, non-coding RNA, and proteomic analyses, enabling multi-dimensional data integration. Experimental validation has demonstrated that this chip achieves single-cell resolution and whole-transcriptome coverage on tissue sections, with a significantly improved gene detection rate.
Option 2: Silica Microsphere Synthesis System—Breaking Through the Limits of Ultra-Long Oligonucleotide Synthesis
This patent utilizes silica microspheres with a specific structure as the synthesis support, combined with an optimized chemical reagent system, to achieve efficient, high-purity one-step synthesis of ultra-long oligonucleotides. The core breakthroughs are reflected in:
1. Innovative Carrier Material Design:Solid silica microspheres with a specific surface area of less than 1 m²/g (preferably with a particle size of 50–100 μm) are selected to replace traditional controlled pore glass (CPG) supports, significantly reducing non-specific adsorption and side reactions. Meanwhile, linker groups containing alkoxy, alkylene chains, and polyethylene glycol (PEG) segments are modified on the microsphere surface to enhance the coupling efficiency with nucleoside phosphoramidite monomers and improve reaction accessibility.
2. Optimized Chemical Reagent System:Developed a composite deprotecting agent system composed of trichloroacetic acid, dichloroacetic acid, and 3,5-dinitrobenzoic acid to efficiently remove protecting groups while minimizing chain damage; employed a combination of 5-benzylthio-1H-tetrazole-N-methylimidazole and 4,5-dicyanoimidazole in the coupling reaction to enhance reaction rate and specificity.
3. Innovations in High-Efficiency Synthesis Units:Replacing traditional monomers with nucleoside phosphoramidite polymers (dimers, trimers, or tetramers) significantly reduces the number of synthesis cycles. For instance, synthesizing a 300-nt strand using trimers requires only 100 cycles, which shortens synthesis time by 40% and reduces reagent consumption by 50% compared to conventional methods. This approach also minimizes the accumulation of side reactions and increases the proportion of full-length products. Case studies demonstrate that this system has successfully synthesized ultra-long oligonucleotides up to 329 nt in length, with purity significantly superior to that achieved by traditional methods.
From research laboratories to industrial applications, the two patented technologies developed by Shi Yongyong’s team have not only resolved core technical bottlenecks in current life sciences research but also, through collaboration with Dynasty Gene, established a complete pipeline for “technology R&D to achievement commercialization.”
Nevertheless, in the face of these challenges, global biotechnology companies are also making active breakthroughs in foundational technologies. By innovating spatial encoding strategies and long-chain synthesis processes, they are targeting the performance ceilings of existing technologies, thereby forming distinct industrial layouts.
In the field of spatial omics,Bruker CorporationAs a global leader in scientific instruments and technology solutions, the company focuses its core strategy on spatial biology, dedicated to providing key tools for research in oncology, neuroscience, and other fields, as well as for the translation of precision medicine, through high-resolution, high-throughput spatial omics technology platforms. In the spatial omics market, Bruker has launched four core technical products/upgrade solutions, each with clear positioning, functionality, and development stages.
To accelerate technology implementation, Bruker is simultaneously advancing supporting infrastructure and strategic partnerships: designed for high-throughput CosMx SMI users“Sapphire Space Program”Entered the pilot phase, offering premium services including dedicated concierge support, performance monitoring tools, and expert guidance, with expansion planned for late 2025; expanded partnership with Weill Cornell Medicine"Spatial Atlas of Human Anatomy (SAHA)"Project collaboration to jointly construct multicellular, single-cell, and subcellular atlases of 30 non-diseased organs from healthy adults; a global initiative will be launched in March 2025“Galaxy Space Journey”Educational Seminar: Building a Platform for Direct Engagement Between Customers and Spatial Biology Experts.
BGI Spatial OmicsOutstanding achievements. They have developed Stereo-seq, a globally leading spatiotemporal omics technology that achieves both “nanoscale resolution” and a “centimeter-scale panoramic field of view.” Leveraging this core technology, BGI Spatiotemporal Omics has launched multiple mature solutions.
For fresh frozen samples, they have developedSpatial Transcriptomics FF V1.3. Currently, the product is officially open for pre-order in the research sector and has been put into practical use. For formalin-fixed paraffin-embedded (FFPE) samples commonly encountered in clinical practice, a corresponding spatial transcriptomics FFPE solution has also been developed. This solution enables in-depth exploration of the spatial gene expression value of archived clinical samples and is currently in the stage of commercial application.
The team has also developed large-format spatial transcriptomics chips specifically designed for large tissue samples. These chips meet the needs of spatial mapping for organ-scale and other large tissues, and have already supported multiple related research projects. In addition, Stereo-CITE, a spatial proteo-transcriptomics platform, is highly competitive; it enables simultaneous analysis of gene expression and protein levels, providing a powerful tool for multi-omics spatial resolution, and is currently in the stage of commercial application.
In the field of gene synthesis,Beijing Tsingke Biotechnology Co., Ltd.As a national-level technology enterprise in the field of synthetic biology, it focuses on the layout of the entire gene synthesis industry chain. Its products and technologies have formed a mature and comprehensive system, all of which are in the stage of commercial application or stable service, covering multi-dimensional core links.
Two platform-level technological breakthroughs developed by Professor Shi Yongyong’s team at Shanghai Jiao Tong University have provided a more robust foundational toolkit for life sciences research and precision medicine practice, addressing the fields from the dual dimensions of molecular synthesis sources and spatial information analysis. These advancements are also highly aligned with current global and domestic industrial innovation trends. Against the backdrop of fierce competition among global biotechnology companies to overcome technical bottlenecks, the commercialization of these two patented technologies through collaboration with Dynasty Gene has not only filled technological gaps in related fields within China but also provided core support for local enterprises to compete on the international stage.