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AVIPure dsRNA Clear Resin
AVIPure® dsRNA Clear affinity resin delivers >100‑fold dsRNA reduction while maintaining high target mRNA yield. Available pre-packed in OPUS® columns, this flow-through affinity chromatography solution eliminates immunogenic dsRNA byproducts to improve the safety of mRNA therapeutics and vaccines.
product features
Improved product purity and safety
Easy and effective dsRNA clearance
Shown to eliminate immunogenicity when paired with optimized IVT
Supports safety and efficacy of mRNA therapeutic
High target mRNA yield
High dsRNA specificity with low mRNA binding
Outperforms traditional dsRNA removal methods
High performance and efficiency
Scalable
Flow-through affinity chromatography
Fully aqueous—no heating or solvents required
Fits diverse mRNA workflows
Available in OPUS® pre-packed columns
Effective dsRNA removal for improved mRNA product purity
Double-stranded RNA (dsRNA) is a common byproduct of in vitro transcription (IVT) protocols used in mRNA manufacturing. Efficient removal of immunogenic dsRNA is essential to ensure the safety and efficacy of mRNA biotherapeutics. AVIPure dsRNA Clear affinity resin is the first and only bead-based affinity chromatography solution for removing dsRNA impurities from mRNA preparations. The resin delivers precise and reliable removal of dsRNA from single-stranded RNA (ssRNA). Studies have demonstrated that, when combined with optimized IVT processes, AVIPure dsRNA Clear can achieve elimination of immunogenicity, even with standard (unmodified) nucleotides. Available pre-packed in OPUS® chromatography columns, AVIPure dsRNA sets a new standard for scalable dsRNA removal in mRNA production processes.
What is dsRNA contamination in mRNA manufacturing?
dsRNA is a critical impurity that presents several challenges for mRNA producers. This highly immunogenic byproduct of IVT triggers inflammation and the body’s anti-viral response. The resulting increase in side effects can warrant a lower dose in the mRNA therapeutic administered, resulting in reduced efficacy. Therefore, maximal efficacy in vivo requires control of dsRNA during the manufacturing process. Furthermore, while dsRNA makes up only 0.1% of total RNA, it is similar in size, length, and sequence to mRNA, making it difficult to detect and remove from mRNA feeds. AVIPure dsRNA Clear offers a solution to this challenge that is easy to implement and scale.
Selective dsRNA removal
Affinity purification using the AVIPure dsRNA Clear resin has been shown to selectively remove dsRNA and reduce dsRNA levels by >100-fold, to as low as 0.00007% w/w of total mRNA, with no negative impact on RNA integrity. Because the resin operates in flow-through mode, no separate elution step is required, allowing for quick and effective removal of dsRNA from mRNA feedstocks.
The combination of optimized IVT and AVIPure dsRNA Clear has been shown to successfully eliminate immunogenicity, as demonstrated by a Luciferase reporter cell line assay. RNA was synthesized with standard (unmodified) nucleotides.
Eliminate immunogenicity in mRNA therapeutics
Even for labs that have already optimized IVT processes to manage the production of dsRNA byproducts, the AVIPure dsRNA Clear resin offers a clear benefit. In a published study, only the combination of optimized IVT and AVIPure dsRNA Clear resin successfully eliminated immunogenicity, inducing no inflammatory response in a reporter cell line assay. The purified RNA, synthesized with standard nucleotides, induced greater protein expression and healthier cells.1
Eliminate immunogenicity in mRNA therapeutics
Even for labs that have already optimized IVT processes to manage the production of dsRNA byproducts, the AVIPure dsRNA Clear resin offers a clear benefit. In a published study, only the combination of optimized IVT and AVIPure dsRNA Clear resin successfully eliminated immunogenicity, inducing no inflammatory response in a reporter cell line assay. The purified RNA, synthesized with standard nucleotides, induced greater protein expression and healthier cells.1
The combination of optimized IVT and AVIPure dsRNA Clear has been shown to successfully eliminate immunogenicity, as demonstrated by a Luciferase reporter cell line assay. RNA was synthesized with standard (unmodified) nucleotides.
Strategies for dsRNA Removal and Accurate Quantitation in Emerging mRNA Modalities
Discover how pairing the AVIPure dsRNA Clear resin with optimized IVT processes can successfully eliminate immunogenicity in this webinar with Dr. Kelsey Swingle, Assistant Professor at Rice University and Dr. Nathaniel Clark, Senior Scientist at Repligen.
“This is going to change the industry.”
–Multinational biopharmaceutical organization
“AVIPure dsRNA Clear resin provided a practical and effective flowthrough-mode option for reducing dsRNA in mRNA processes while maintaining strong product recovery. Across multiple constructs, including both linear and circular RNA, we observed consistent dsRNA clearance from load to flowthrough. Repligen provided excellent technical support throughout the evaluation.”
–Heather Mallory, PhD
Senior Scientist, Downstream Process Development at Recipharm
“Best technology we’ve seen so far.”
–Large global contract development manufacturing organization (CDMO)
“We’ve tried many methods to remove dsRNA. This one is by far the best.”
–European CDMO focused on mRNA development
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Techniques for measuring and removing dsRNA byproducts from IVT RNA
Double-stranded RNA byproducts can trigger unwanted immune responses, representing a significant concern for RNA therapeutics. Measuring dsRNA contaminants and subsequently removing them are key to ensuring the safety and efficacy of mRNA, circRNA, and saRNA therapeutics.
Selective removal of immunogenic double-stranded RNA from mRNA feeds using affinity chromatography
This article describes the design and construction of the AVIPure dsRNA Clear affinity resin, summarizes the size distribution of dsRNA byproducts measured by immuno-northern blotting, and outlines a high-throughput filter-plate workflow to optimize binding conditions.
A scalable purification strategy for removal of dsRNA byproducts
This article describes the development, validation, and application of the AVIPure dsRNA Clear affinity resin to remove immunogenic dsRNA impurities in mRNA therapeutics.
An immuno-northern technique to measure the size of dsRNA byproducts in IVT RNA
This article describes a method for determining the sizes of dsRNA byproducts in mRNA feed streams, developed by Repligen scientists.
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High mRNA recovery
The AVIPure® dsRNA Clear affinity ligand is specific for the RNA double helix. The resin selectively binds dsRNA in moderate to high salt conditions (>0.5 M NaCl) from pH 7.2-9.5 for easy impurity removal, allowing mRNA, circular RNA, and self-amplifying RNA to flow through. This selectively results in minimal mRNA binding, enabling high target mRNA recovery. A residual ligand ELISA kit available for detection of leached ligand.
AVIPure dsRNA Clear outperforms traditional methods
Current methods for removing dsRNA include cellulose and reverse-phase high-performance liquid chromatography (RP-HPLC). Cellulose is difficult to pack in a chromatography column and uses large volumes of ethanol, requiring significant controls to mitigate combustion risk. RP-HPLC also requires heat and large volumes of organic solvents. Both methods are difficult to scale and compromise mRNA recovery.
In contrast, AVIPure dsRNA Clear resin outperforms both methods, while maintaining high mRNA recovery. In one study, the affinity resin achieved a 270-fold (2.4) log reduction in dsRNA levels. In comparison, the cellulose treatment reduced dsRNA by 13-fold and RP-HPLC by 58-fold.1 At the same time, the affinity resin yielded 94% mRNA recovery, compared to 73% for cellulose.
Demonstrated high mRNA yield
In this customer case study, a well-known mRNA developer uses AVIPure dsRNA Clear to achieve significant dsRNA reduction to specification levels while maintaining excellent mRNA recovery.
Dramatic reduction in dsRNA levels
The customer reports that they have experienced consistent reduction of dsRNA levels to meet their specifications.
Over 90% mRNA yield
The customer consistently achieves greater than 90% mRNA yield with the AVIPure dsRNA Clear resin
Consistent scale-up performance
The performance of the customer's 50 mL OPUS® ValiChrom® column compares well to the 10 mL OPUS® MiniChrom® column.
Scalable, flow-through chromatography solution
The AVIPure dsRNA Clear resin uses innovative HiPer™ base bead technology. This macroporous bead structure allows for convective flow both around and through the beads, maximizing surface area for high dynamic binding capacity while also supporting rapid flow-through. This resin has a dynamic binding capacity of ≥0.4 mg dsRNA/mLcolumn volume at 10% breakthrough, achieving high volumetric throughput with optimal clearance with 1-minute residence time.
No heating or solvents required
Unlike traditional methods for dsRNA removal, the AVIPure dsRNA Clear affinity resin does not require solvents or heating. Only aqueous buffers are required.
Flexibility to fit diverse mRNA workflows
The AVIPure dsRNA Clear resin can be used either before or after poly-dT purification, depending on your process requirements.
Flexibility to fit diverse mRNA workflows
The AVIPure dsRNA Clear resin can be used either before or after poly-dT purification, depending on your process requirements.
Maximize efficiency with AVIPure dsRNA Clear in OPUS columns
AVIPure dsRNA Clear resin is available exclusively in OPUS® pre-packed columns, from process development to large scale for GMP production. GMP-ready columns are available today in standard diameters from 2.5 cm to 25 cm, with larger formats available following engineering review. Ready to take the next step? • Order now: Visit our e-store to evaluate AVIPure dsRNA Clear today. • Speak with a technical specialist: Complete the form to discuss your needs and get expert guidance.
Absolutely. IVT optimization certainly helps to lower dsRNA and reduce immunogenicity, but as demonstrated by Clark et al., IVT optimization combined with affinity purification produces a much larger result. Putting the two techniques together resulted in mRNA—made with standard nucleotides—that was completely non-immunogenic compared to baseline.
Yes, it does. Repligen customers have successfully processed saRNA using this resin. Due to the HiPer base bead structure, even with very large molecules, you can use a fast flow rate and obtain excellent mass transfer.
Yes, AVIPure dsRNA Clear also has been shown to be successful at clearing dsRNA from circRNA preparations as well.
Reference
- Clark N, Kozarski M, Asci S, et al. Removal of dsRNA byproducts using affinity chromatography. Molecular Therapy Nucleic Acids, 2025; 36(2):102549.
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