Spatial Transcriptomics: The New Frontier of RNA Therapeutics

RNA therapeutics are ushering in a new era in medicine, offering precise and effective treatments for a wide range of diseases.

Previously, in “The Critical Role of Bioinformatics in the Development of RNA Therapeutics,” we discussed how Via Scientific’s platform, Via Foundry, empowers scientists to harness the potential of RNA molecules. In “RNA Therapeutics: Current Challenges and Emerging Trends,” we explored the various obstacles and advancements in the field. Today, we venture into the innovative realm of spatial transcriptomics — a groundbreaking approach that adds a critical spatial dimension to multi-omics, revolutionizing RNA therapeutics.

Understanding Spatial Transcriptomics

Spatial transcriptomics is transforming our understanding of cellular function and disease pathology. Spatial transcriptomics is an advanced technique that allows scientists to map gene expression within the spatial context of tissues. This method provides an unprecedented level of detail, enabling researchers to see exactly where specific genes are active within the complex architecture of tissues.

By adding the spatial dimension, researchers can now visualize gene expression within the physical layout of tissues, offering insights that were previously unattainable. This technique is akin to having a GPS for the cellular landscape, guiding researchers to precise locations of gene activity and interactions.

The Importance of Spatial Transcriptomics in RNA Therapeutics

Detailed Cellular Landscape

Spatial transcriptomics provides precision mapping of cellular interactions and molecular landscapes within tissues. This high-resolution approach reveals the heterogeneity of cell populations at single-cell resolution, offering insights that are not possible with traditional bulk analysis methods.

Insights into Disease Mechanisms

Understanding the spatial distribution of gene expression changes within diseased tissues enables researchers to better understand and discover both the underlying disease mechanisms and helps them to identify targets for cellular taregting. This knowledge is essential for developing targeted RNA therapeutics that can effectively address the root causes of diseases.

Enhanced Drug Development

By pinpointing the exact location of gene expression changes, spatial transcriptomics amplifies the ability of researchers to develop RNA therapeutics with improved efficacy and safety. This is because spatial precision enables a reduction in off-target effects, leading to more effective treatments.

Integration with Multiomics Data

Combining spatial transcriptomics with other omics data (genomics, proteomics, metabolomics) provides researchers with a holistic view of the underlying biological processes. This integrated approach offers deeper insights into cellular functions and disease mechanisms, further facilitating the discovery of novel therapeutic targets and biomarkers.

How Spatial Transcriptomics Works

Spatial transcriptomics involves positioning tissue samples on glass slides containing spatially barcoded oligonucleotides. These barcodes capture mRNA molecules released from the tissue, preserving the spatial location of each gene’s activity. The captured mRNA is then sequenced, and the data is mapped back to its original location in the tissue, creating a detailed spatial map of gene expression.

The first widely adopted method, described by Ståhl et al. in 2016, involves placing tissue samples on glass slides with “spots” of spatially barcoded oligo(dT) tails that capture poly-adenylated mRNAs. The tissue is fixed, stained, and enzymatically permeabilized to release RNA, which then hybridizes to the oligo(dT) probes. Reverse transcription is carried out in situ, synthesizing spatially marked cDNA. This cDNA is used to create sequencing libraries, which are then analyzed to provide a map of gene expression within the tissue sample.

Applications of Spatial Transcriptomics

Disease Research

Defining the spatial distribution of mRNA molecules allows for the detection of cellular heterogeneity in tissues and tumors. This is critical for understanding cancer progression, immune responses, and other complex biological processes.

Developmental Biology

Spatial transcriptomics offers insights into embryonic development by revealing how gene expression patterns change over time and across different regions of developing tissues.

Neurology

Mapping gene expression within brain tissues helps researchers understand neurological disorders and identify specific cell types and regions involved in diseases like Alzheimer’s and Parkinson’s.

Personalized Medicine

Spatial transcriptomics further acclerates the development of personalized therapies by providing detailed maps of gene expression in individual patients, allowing for treatments tailored to the specific molecular landscape of their tissues.

How Via Foundry Supports Spatial Transcriptomics

Via Foundry provides a comprehensive platform for integrating and analyzing spatial transcriptomics data, offering several unique advantages:

Comprehensive Data Fusion & Integration

Via Foundry seamlessly integrates spatial transcriptomics data with other omics data, providing a unified view of biological processes. This fusion of spatial information with other molecular data enables researchers to gain a signifcantly more comprehensive understanding of underlying biology which is critical to effectively acclerate theraputic candidates.

Advanced Analysis Tools

Via Foundry offers robust bioinformatics pipelines for spatial data analysis, including quality control, contamination checks, and advanced visualization techniques. These tools are designed to handle complex datasets and provide actionable insights, accelerating research and development.

Customizable Workflows

Via Foundry supports both automated and manual (command-line) data processing options, catering to researchers with varying levels of expertise. This flexibility allows scientists to effectively utilize spatial transcriptomics data according to their specific needs.

Enhanced Visualization

Via Foundry’s powerful visualization tools map gene expression data onto tissue sections, enabling researchers to explore spatial relationships and patterns easily. This capability is crucial for understanding the spatial context of gene activity and its implications for disease mechanisms.

Comprehensive Data and Metadata Management

Via Foundry ensures that all data, including spatial transcriptomics, is managed within a unified and normalized framework. This comprehensive data and metadata management approach facilitates better data integration, analysis, and reproducibility, enhancing the reliability of research findings.

Case Studies and Real-World Applications

To illustrate the transformative potential of spatial transcriptomics and Via Foundry, let’s explore some real-world applications and case studies.

Case Study 1: Cancer Research

In cancer research, spatial transcriptomics has been used to map the heterogeneity of tumor microenvironments. By integrating spatial data with other omics data in Via Foundry, researchers have identified specific cell populations and their interactions within tumors. This has led to the discovery of novel therapeutic targets and the development of more effective, targeted RNA therapeutics.

Case Study 2: Neurological Disorders

Researchers studying neurological disorders have utilized spatial transcriptomics to map gene expression within brain tissues. Via Foundry’s advanced analysis tools have enabled these researchers to quickly identify distinct neuronal populations and understand their roles in diseases such as Alzheimer’s and Parkinson’s. This has opened new avenues for developing RNA-based treatments tailored to specific neuronal subtypes.

Case Study 3: Personalized Medicine

In personalized medicine, spatial transcriptomics provides detailed maps of gene expression in individual patients. Via Foundry has facilitated the integration of this spatial data with other omics data, allowing researchers to develop personalized RNA therapeutics. These tailored treatments offer improved efficacy and reduced side effects, enhancing patient outcomes.

Conclusion

Spatial transcriptomics is transforming the development of RNA therapeutics by providing detailed maps of gene expression within tissues. Via Foundry’s advanced tools and comprehensive data integration capabilities make it an indispensable platform for researchers leveraging the power of spatial transcriptomics. By offering integrated, customizable, and advanced solutions, Via Foundry ensures that researchers can navigate the complex landscape of cellular biology with precision and clarity, driving innovations in RNA therapeutics.

As the field of RNA therapeutics continues to evolve, the ability to accurately map and analyze gene expression within tissues will be crucial for developing effective treatments. With Via Foundry, researchers are empowered to overcome the toughest challenges in RNA therapeutics, accelerating the journey from discovery to groundbreaking patient care.