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Custom saRNA Synthesis Service

Introduction saRNA Synthesis Workflow What We Can Offer Case Study FAQ

Introduction

Small activating RNA (saRNA) uses RNA activation (RNAa) to upregulate endogenous gene expression. As short double-stranded RNA targeting gene promoters, it recruits the RITA complex as an "ON switch" and may reverse epigenetic silencing of tumor suppressor genes. Custom saRNA Synthesis Service offers high-purity, validated saRNA via proprietary RNAa sequence design and advanced LNP formulation to accelerate therapeutic development.

Creative Biolabs' service provides tools to restore underexpressed/silenced target gene function, delivers high-specificity RNAa molecules with a unique "ON switch" for tough targets, and covers solutions from design and modification to delivery.

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Custom saRNA Synthesis Service

saRNA

Small Activating RNA (saRNA) is a synthetic, double-stranded oligonucleotide typically 21 to 30 nucleotides in length. It is chemically distinct from siRNA (which silences genes) and mRNA (which translates protein) because its primary function is to directly initiate and enhance the transcription of target genes, rather than mediating degradation or providing a template for translation.

Main steps of the saRNA replication cycle within the host cell. (OA Literature)Fig.1 The replication cycle and main steps of saRNA in host cells.1

Mechanism

The underlying principle is RNA activation (RNAa). The saRNA molecule is designed to bind to a specific region within the promoter of a target gene. Once bound, it initiates the recruitment of the RITA complex, which is believed to include transcription factors and chromatin-modifying enzymes. This activity promotes an open chromatin state and stimulates the cell's own machinery to increase the transcription rate of the targeted gene, thus leading to the upregulation of the corresponding protein product.

Advantages

The use of saRNA offers several distinct advantages for therapeutic development:

  • Restoration of Natural Function: saRNA works by activating the native gene, ensuring the expressed protein is produced, regulated, and modified naturally within the cell, retaining its full, complex function.
  • Long-Lasting Effect: By initiating sustained transcriptional activation at the promoter site, saRNA often exhibits a long-lasting effect after a single dose compared to the transient nature of standard mRNA or protein delivery.
  • No Genomic Alteration: Since saRNA acts on the existing genomic sequence and does not require integration or introduction of exogenous DNA, it fundamentally minimizes the risk of unintended genomic side effects.
  • Design Flexibility: The ability to incorporate specialized chemical modifications (e.g., Cap 1, modified nucleosides) allows for precise tuning of stability and activity tailored to the intended in vivo application and specific target tissue.

Workflow

The typical timeframe for this service ranges from 8 to 14 weeks, depending on the complexity of the target gene and the required modification/formulation scope.

Required Starting Materials Key Steps Involved Final Deliverables
Target Gene Sequence: Full genomic sequence, including the promoter region. Target Validation & Design
Creative Biolabs experts identify optimal activation regions and use proprietary ML algorithms to design specific saRNA sequences (optimizing length, GC content, secondary structure).
Final Purified saRNA Product: GMP-grade or Research-grade purified saRNA oligonucleotide (e.g., 1 mg to 1 g scale).
Target Cell Line: Information on the expression context (e.g., cancer cell line, primary tissue) for validation. Custom Modification & Synthesis
Incorporate chemical modifications (e.g., N1-methylpseudouridine, Cap 1) to boost stability and translation efficiency, followed by advanced solid-phase or enzymatic synthesis.
Characterization Report: Detailed data on purity (≥95%), sequence confirmation, molecular weight analysis, and LNP characterization (size, zeta potential, encapsulation efficiency).
Delivery Strategy Preference (if any): E.g., desired LNP composition or targeting ligand for conjugation. LNP Formulation & Encapsulation
Purified saRNA is encapsulated into optimized LNPs via microfluidics, ensuring consistent size and high encapsulation efficiency for optimal in vivo delivery.
Functional Validation Data: Results from in vitro assays (qPCR and Western Blot) demonstrating confirmed target gene activation and protein upregulation in the client's supplied cell system.
Functional Assessment & Optimization
LNP samples undergo comprehensive stability analysis and cell-based activity testing. Optimization adjusts LNP composition (ICLs vs. PCLs) or saRNA modifications based on performance.

What We Can Offer

Creative Biolabs offers an unparalleled, fully integrated service dedicated to accelerating your next-generation saRNA therapeutic development. We don't just synthesize—we provide a de-risked path to clinical readiness, managed by industry experts.

Integrated End-to-End Development

A streamlined, one-stop service covering everything from proprietary saRNA sequence design, high-fidelity synthesis, and sophisticated LNP formulation to comprehensive functional validation.

Precision Design and Activation

Utilization of our advanced RNA Activation (RNAa) design platform and Machine Learning tools to generate saRNA with guaranteed specificity for optimal target promoter binding and robust gene upregulation.

Advanced LNP Delivery Optimization

Custom formulation using next-generation, low-toxicity Ionizable Cationic Lipids (ICLs), ensuring maximized cellular uptake and efficient cytosolic release—the key to effective in vivo saRNA delivery.

Custom Chemical Modification

Expert selection and incorporation of stability-enhancing modifications (e.g., Cap 1, N1-methylpseudouridine) tailored to your specific application to maximize in vivo half-life and minimize off-target immune responses.

Scalable GMP-Ready Production

Flexible, high-capacity synthesis from research-scale batches to GMP-grade, large-scale production (gram-scale), providing a seamless transition pathway from discovery to preclinical and clinical trials.

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Case Study

saRNA Design

Schematic diagram of the genomic structure of the capped saRNA designed. (OA Literature)Fig.2 Schematic diagram of the genomic structure of capped saRNA.2

Transfection Efficiency

The infection of HEK293 by saRNA containing GFP was observed under a fluorescence microscope. (OA Literature)Fig.3 The expression of eGFP in SARNA-EGFP-transfected HEK 293T cells on the 1st, 2nd, and 5th days after transfection.2

Encapsulation Efficiency

The encapsulation of saRNA using LNP has a relatively high encapsulation rate. (OA Literature)Fig.4 The encapsulation efficiency of saRNA-cLNP is relatively high.2

Cytotoxicity

saRNA encapsulated with LNP does not have strong cytotoxicity. (OA Literature)Fig.5 saRNA-cLNP does not have significant cytotoxicity.2

Customer Reviews

  • "High Purity & Consistency." Using Creative Biolabs' Custom saRNA Synthesis in our research has significantly improved the in vitro consistency of our transcription factor upregulation studies. Their promise of Cap 1 structure incorporation truly delivered; we observed a marked reduction in immune response artifacts compared to previous third-party constructs.

    [8 months ago], Dr. Martin Brown

  • "Exceptional LNP Formulation." We were struggling with cytotoxicity using traditional permanently cationic LNP systems for our saRNA. Creative Biolabs' switch to Ionizable Cationic Lipids for encapsulation facilitated a near 80% drop in measured cytotoxicity while maintaining delivery efficiency—a crucial breakthrough for our Phase 0 trials.

    [2 months ago], Prof. Lynn Carter.

  • "Precise Gene Activation." Creative Biolabs' saRNA design platform provided the highly specific promoter targeting we needed to restore the expression of a tumor suppressor gene. The qPCR data they supplied with the final product were highly valuable and completely supported our in vivo observations, confirming their commitment to functional validation.

    [1 year ago], David Harris

FAQs

Q: What type of gene targets is Creative Biolabs' saRNA most effective for, and can it be used for knockdown instead of activation?

A: Our saRNA is specifically designed for gene activation, making it ideal for targets that are underexpressed or silenced (e.g., tumor suppressors, developmental factors). If your goal is gene knockdown, we recommend inquiring about our robust Custom siRNA Synthesis Service, which is optimized for RNA interference (RNAi) and is highly effective for silencing.

Q: How does Creative Biolabs address the delivery and stability challenges associated with using RNA in vivo?

A: We tackle delivery through our specialized LNP formulation services. We prioritize Ionizable Cationic Lipids (ICLs), which offer superior in vivo safety profiles compared to permanently charged lipids. For stability, we incorporate proprietary chemical modifications like Cap 1 structures and modified bases during synthesis, which are proven to enhance the half-life and translational longevity of the saRNA.

Q: Is there a risk of our custom saRNA product generating infectious particles?

A: Small Activating RNA (saRNA), which is the focus of this service, does not carry any risk of generating infectious particles as it does not contain the viral replicase genes necessary for self-amplification. However, if your project requires Self-Amplifying RNA (saRNA) for vaccine purposes, Creative Biolabs employs advanced safety strategies like the Trans-Amplifying RNA (taRNA) system to specifically mitigate any recombination risk.

Q: We need to scale up for preclinical trials. What is the production capacity of Creative Biolabs' service?

A: Our synthesis platform is fully scalable, supporting batch sizes ranging from small research-grade quantities (milligrams) up to large-scale, high-yield GMP production (gram-scale) required for IND-enabling studies and early clinical phases. The specific turnaround time and cost will depend on the final required scale and complexity of modifications. Please contact us to discuss your scale-up requirements.

Creative Biolabs is your end-to-end partner for next-generation nucleic acid therapeutics. Our Custom saRNA Synthesis Service empowers you to precisely control endogenous gene expression, backed by industry-leading expertise in LNP formulation and comprehensive RNA engineering. We provide the quality, validated product, and strategic insight required to accelerate your project from bench to clinic.

Contact Our Team for More Information and to Discuss Your Project

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References

  1. Vallet, Thomas, and Marco Vignuzzi. "Self-amplifying RNA: advantages and challenges of a versatile platform for vaccine development." Viruses 17.4 (2025): 566. https://doi.org/10.3390/v17040566. Distributed under Open Access license CC BY 4.0, without modification.
  2. Kairuz, Dylan, et al. "Production, characterization, and assessment of permanently cationic and ionizable lipid nanoparticles for use in the delivery of self-amplifying RNA vaccines." Pharmaceutics 15.4 (2023): 1173. https://doi.org/10.3390/pharmaceutics15041173. Distributed under Open Access license CC BY 4.0, figures were cropped.
All products and services are For Research Use Only and CANNOT be used in the treatment or diagnosis of disease.