Viral Vector Solutions

Viral Vector Solutions

The Waters suite of analytical solutions is innovative, reliable, sensitive, and robust, enabling comprehensive characterization of viral vectors and providing deeper insights into the integrity, potency, and safety of new modalities. Waters combines chromatography columns and systems, optical and mass analysis detectors, and automated compliance-ready data analysis and reporting tools for turnkey application success.

The Waters suite of analytical solutions is innovative, reliable, sensitive, and robust, enabling comprehensive characterization of viral vectors and providing deeper insights into the integrity, potency, and safety of new modalities. Waters combines chromatography columns and systems, optical and mass analysis detectors, and automated compliance-ready data analysis and reporting tools for turnkey application success.
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Characterize LNPs to ensure product safety and efficacy.
Characterize LNPs to ensure product safety and efficacy.

Overview

Viral vector-based gene therapies are large drug-product formulations comprised of protein and nucleic acid components containing over 200,000 atoms. Waters’ liquid chromatography (LC) combined with optical detection (UV, MALS) and mass spectrometry (MS) provide the analytical means to accurately characterize and quantify these heterogeneous structures and their attributes, at both component and intact levels, supporting robust viral vector solutions. Routine measurements include viral titer, aggregate/impurities analysis, viral protein ratios, peptide mapping & modification analysis, encapsidation efficiency, and genome integrity in your viral vector solution workflows.

Antibodies attacking cell ridden by virus

Applications

Size exclusion chromatography with multiangle light scattering (SEC-MALS) and UV detection enables measurement of multiple AAV attributes, including titer, size-distribution, molar mass, aggregate, and empty/full ratio, critical for optimizing viral vector solutions. Asymmetric field flow fractionation with MALS (FFF-MALS) allows for measurement of larger capsids. Charge detection mass spectrometry (CDMS) provides direct, high-resolution measurement of capsid populations, enabling relative quantification of empty, partial, and full capsids as well as other impurities in viral vector preparations.

Size exclusion chromatography with multiangle light scattering (SEC-MALS) and UV detection enables measurement of multiple AAV attributes, including titer, size-distribution, molar mass, aggregate, and empty/full ratio, critical for optimizing viral vector solutions. Asymmetric field flow fractionation with MALS (FFF-MALS) allows for measurement of larger capsids. Charge detection mass spectrometry (CDMS) provides direct, high-resolution measurement of capsid populations, enabling relative quantification of empty, partial, and full capsids as well as other impurities in viral vector preparations.

Application Notes

AAV capsids are made of three viral proteins that self-assemble in a 1:1:10 ratio. Post-translational modifications (PTMs) can impact product performance. Workflows for PTM & impurities analysis support capsid engineering, process development, and release testing for viral vector solutions.

AAV capsids are made of three viral proteins that self-assemble in a 1:1:10 ratio. Post-translational modifications (PTMs) can impact product performance. Workflows for PTM & impurities analysis support capsid engineering, process development, and release testing for viral vector solutions.

Application Notes

Genome integrity testing verifies that the viral vector genome contains only the intended sequence and is free from mutations or rearrangements. Traditional methods like alkaline gel electrophoresis have been used but offer limited resolution. High-resolution LC-based methods are now preferred for accurate assessment in viral vector preparations.

Genome integrity testing verifies that the viral vector genome contains only the intended sequence and is free from mutations or rearrangements. Traditional methods like alkaline gel electrophoresis have been used but offer limited resolution. High-resolution LC-based methods are now preferred for accurate assessment in viral vector preparations.

Application Notes

High-throughput, comprehensive analysis of aggregates and particles helps you identify and prevent factors that would compromise patient safety or interfere with efficacy. With a combination of dynamic light scattering (DLS) and backgrounded membrane imaging (BMI), you can detect and count particles from 0.5 nm to 5 mm at high throughput with low sample volumes. Fluorescence membrane microscopy (FMM) lets you determine the content and origin of the particles, from extrinsic to protein or nucleic acid. The combination helps you mitigate risks early, optimize stability, and ensure compliance.

High-throughput, comprehensive analysis of aggregates and particles helps you identify and prevent factors that would compromise patient safety or interfere with efficacy. With a combination of dynamic light scattering (DLS) and backgrounded membrane imaging (BMI), you can detect and count particles from 0.5 nm to 5 mm at high throughput with low sample volumes. Fluorescence membrane microscopy (FMM) lets you determine the content and origin of the particles, from extrinsic to protein or nucleic acid. The combination helps you mitigate risks early, optimize stability, and ensure compliance.

Application Notes

ultraDAWN real-time MALS directly monitors product attributes post-purification, enhancing yield and flexibility. It connects downstream purification and enrichment methods, such as IEX, FPLC, or TFF, to measure capsid, genomic titer, size, and impurities in real-time, streamlining processing and maximizing yield for viral vector solutions.

ultraDAWN real-time MALS directly monitors product attributes post-purification, enhancing yield and flexibility. It connects downstream purification and enrichment methods, such as IEX, FPLC, or TFF, to measure capsid, genomic titer, size, and impurities in real-time, streamlining processing and maximizing yield for viral vector solutions.

Application Notes

Webinar: Bridging Innovation and Industry with Charge Detection Mass Spectrometry (CDMS)

In this webinar, Prof. Martin Jarrold (Indiana University), Dr. Ben Clarke (US Pharmacopeia), and Dr. Rebecca D’Esposito discussed the impact of CDMS on the future of biotherapeutic analysis.

In this webinar, Prof. Martin Jarrold (Indiana University), Dr. Ben Clarke (US Pharmacopeia), and Dr. Rebecca D’Esposito discussed the impact of CDMS on the future of biotherapeutic analysis.
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Solutions

Waters LC and LC-MS systems offer leading separations performance and sensitivity for viral vector analysis.

Waters LC and LC-MS systems offer leading separations performance and sensitivity for viral vector analysis.

Unprecedented direct mass measurement for the characterization of mega-mass and heterogeneous biomolecules

Unprecedented direct mass measurement for the characterization of mega-mass and heterogeneous biomolecules
Charge Detection Mass Spectrometry (CDMS)

Charge Detection Mass Spectrometry (CDMS) overcomes the limits of conventional MS by enabling precise, high-throughput mass measurement of intact mega-mass biomolecules directly from a benchtop device.

  • Titer, Aggregates, and Intact Heterogeneity
  • Capsid Engineering & PTM Analysis
  • Genome Integrity

For efficient product attribute monitoring throughout development and manufacturing

For efficient product attribute monitoring throughout development and manufacturing
BioAccord LC-MS System

Enable LC-MS vector attribute analyses in every Development and GxP lab with Waters BioAccord LC-MS System and waters_connect software for compliance-ready data analysis and reporting for viral vector solutions.

  • Capsid Engineering & PTM Analysis

Complete high-resolution coverage for confident characterization

Complete high-resolution coverage for confident characterization
Xevo G3 QTof

Accelerate viral vector characterization with the Xevo G3 QTof high-performance HRMS benchtop system that delivers accurate qualitative and quantitative results.

  • Capsid Engineering & PTM Analysis

QC-friendly multi-attribute monitoring

QC-friendly multi-attribute monitoring
DAWN & ultraDAWN MALS Detectors

Accurately measure viral vector aggregation, genome and capsid titer, and empty/full ratio with Wyatt’s DAWN & ultraDAWN MALS detectors with UV & RI detection post LC or FFF separation.

  • Titer, Aggregates, and Intact Heterogeneity
  • Genome Integrity
  • Aggregates and Particle Analysis
  • Real-Time Analysis

High-throughput, automated dynamic light scattering

High-throughput, automated dynamic light scattering
DynaPro DLS/SLS Plate Reader

Determines multiple CQAs of viral vector for gene therapy, including concentration, degree of aggregation and thermal stability.

  • Aggregates and Particle Analysis

Small Volume Subvisible Particle Characterization

Small Volume Subvisible Particle Characterization
AuraGT

Gain unprecedented insight into gene therapy development with Aura GT. Just 5 µL of sample is all you need to evaluate capsid and viral vector aggregates > 1 µm, so you can identify stability issues early.

  • Aggregates and Particle Analysis

Compliance-ready, networkable applications-based software to streamline LC-MS data acquisition, processing, and reporting.

Compliance-ready, networkable applications-based software to streamline LC-MS data acquisition, processing, and reporting.

Streamline data analysis and processing

Streamline data analysis and processing
waters_connect for biopharmaceuticals

Accelerate the journey from sample analysis to decision-making with waters_connect for biopharmaceutical and viral vector solutions analysis, with apps for intact mass analysis, sequence confirmation, process monitoring, and more.

  • Titer, Aggregates, and Intact Heterogeneity
  • Capsid Engineering & PTM Analysis
  • Genome Integrity
  • Real-Time Process Monitoring

Simplify data acquisition, processing, and reporting

Simplify data acquisition, processing, and reporting
Empower Chromatography Data System (CDS)

Equip your lab with Empower Chromatography Data System (CDS) and gain advanced laboratory data management for your viral vector analyses, including acquisition, processing, and reporting.

  • Capsid Engineering & PTM Analysis
  • Genome Integrity
  • Aggregates and Particle Analysis

Turn your data into results with the ultimate in light scattering software

Turn your data into results with the ultimate in light scattering software
ASTRA

Instrument control, data acquisition, analysis and reporting are all provided by ASTRA software with the Viral Vector Analysis module. We provide a platform SEC-MALS method, specifically built for AAV quantitation, that is easily customizable for every product and serotype.

  • Titer, Aggregates, and Intact Heterogeneity
  • Aggregates and Particle Analysis
  • Genome Integrity

Columns for size exclusion, ion exchange and reversed phase chromatography.

Columns for size exclusion, ion exchange and reversed phase chromatography.

Widepore SEC columns for viral vector separations

Widepore SEC columns for viral vector separations
GTxResolve Premier SEC Columns

Enable measurement of multiple attributes, including aggregation & size variant analysis with Waters high efficiency GTxResolve Premier SEC columns that speed analysis time and lower sample consumption.

  • Genome Integrity
  • Aggregates and Particle Analysis
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Anion exchange (AEX) for measuring encapsidation efficiency in viral vector solutions

Anion exchange (AEX) for measuring encapsidation efficiency in viral vector solutions
AEX Columns for Gene-based Therapeutics (GTx)

Improve recovery with Waters AEX chromatography that uses a non-porous, high efficiency stationary phase (e.g.:Protein-Pak Hi Res Q) combined with optimized salt gradients for a QC-friendly technique for empty/full measurements.

  • Titer, Aggregates, and Intact Heterogeneity
  • Genome Integrity
  • Titer, Capsid Empty-Partial-Full Ratio
  • Capsid Engineering & PTM Analysis
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RPLC Columns for viral protein analyses

RPLC Columns for viral protein analyses
MaxPeak Premier BEH C4 RPLC Columns

Identify and measure the relative abundance of viral proteins using MaxPeak Premier BEH C4 columns with DFA ion pairing for optimal LC and MS performance. 

  • Enhanced Separations
  • Titer, Aggregates, and Intact Heterogeneity
  • Capsid Engineering & PTM Analysis

Unique selectivity for measuring PTMs

Unique selectivity for measuring PTMs
GTxResolve BEH Amide Columns

Amide stationary phase designed for high batch to batch reproducibility of viral vectors, capsid proteins, and nucleic acids. Oxidized and phosphorylated variants can be readily resolved from their unmodified counterparts with an optimally applied HILIC separation.

  • Capsid Engineering & PTM Analysis

RPLC columns for viral vector peptide mapping

RPLC columns for viral vector peptide mapping
MaxPeak Premier CSH C18 RPLC Columns

Confirm the sequence, post translational modification (PTMs), or degradation of viral proteins using peptide mapping and Waters CSH™ columns that deliver high resolution for this application.

  • Capsid Engineering & PTM Analysis

Your success is just a click away

Your success is just a click away
Waters Global Services

Optimize your laboratory's productivity and success with Waters Global Services to maintain peak system performance, minimize down time, address application challenges, and support stringent compliance requirements.

  • Titer, Capsid Empty-Partial-Full Ratio
  • Capsid Engineering & PTM Analysis
  • Genome Integrity
  • Aggregates and Particle Analysis
  • Real-Time Process Monitoring

Make science more accessible with Waters Capital

Make science more accessible with Waters Capital
Payment Solutions

Maximize resources and minimize risk with payment options from Waters Capital, including upgrading aging equipment, getting customized support, and bundling services into one monthly payment.

  • Titer, Capsid Empty-Partial-Full Ratio
  • Capsid Engineering & PTM Analysis
  • Genome Integrity
  • Aggregates and Particle Analysis
  • Real-Time Process Monitoring

The data speaks for itself

The data speaks for itself
a) Overlayed mass spectrum of AAV8 zoomed into to the 2.5–6 MDa mass range with 100 % empty, and full capsid treated with 30-minute incubations at 4, 22, 35, and 50 °C. b) Charge spectrum of AAV8 zoomed into the 2.5–6 MDa mass range with 100 % empty, and full capsid treated with 30-minute incubations at 4, 22, 35 and 50 °C

a) Overlayed mass spectrum of AAV8 zoomed into to the 2.5–6 MDa mass range with 100 % empty, and full capsid treated with 30-minute incubations at 4, 22, 35, and 50 °C. b) Charge spectrum of AAV8 zoomed into the 2.5–6 MDa mass range with 100 % empty, and full capsid treated with 30-minute incubations at 4, 22, 35 and 50 °C.

Full (blue) and empty (red) titers determined by RT-MALS during elution (34 – 48 minutes) and strip (> 48 minutes) in the final linear gradient. Buffer ionic strength is represented by the dashed black line

Full (blue) and empty (red) titers determined by RT-MALS during elution (34–48 minutes) and strip (> 48 minutes) in the final linear gradient. Buffer ionic strength is represented by the dashed black line.

Zoomed views of an AAV2 chromatogram as obtained with stainless- steel hardware (4.6 x 150 mm, 5 µm particle, red trace) versus MaxPeak HPS hardware (XBridge Premier GTx BEH SEC 450 Å 2.5 µm 4.6 x 150 mm Column, black trace). Separations were performed with a mobile phase containing a standard ionic strength buffer (10 mM phosphate pH 7.4 + 200 mM KCl).

Relative quantification of VP proteins was measured by optical detection, including (A) UV and (B) Fluorescence (FLR). Peak annotation shows the assignment and calculated relative abundance of the detected components. With FLR detection, the S/N of VP3 is almost five times higher than the S/N of using UV detection with a 10-fold higher mass load, suggesting an approximately 50-fold improvement in sensitivity.

Webinars and Resources

  • eBook

Characterizing AAVs

Characterizing AAVs
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  • Journal Citations

Interlaboratory Measurement of Adeno-Associated Virus: Comparative Quantification of Full and Empty Capsids

Interlaboratory Measurement of Adeno-Associated Virus: Comparative Quantification of Full and Empty Capsids
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  • On Demand Webinar

Fast but Sure AAV Aggregate Analysis with Platform Size Exclusion Methods

Fast but Sure AAV Aggregate Analysis with Platform Size Exclusion Methods
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  • On Demand Webinar

Charge Detection Mass Spectrometry: From Complexity to Clarity – A New Era in Biomolecular Analysis

Charge Detection Mass Spectrometry: From Complexity to Clarity – A New Era in Biomolecular Analysis
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  • On Demand Webinar

Bridging Innovation and Industry with Charge Detection Mass Spectrometry (CDMS)

Bridging Innovation and Industry with Charge Detection Mass Spectrometry (CDMS)
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  • On Demand Webinar

Pushing the boundaries of analytical development and quality control for safer and cleaner products especially in Gene and Cell Therapies

Pushing the boundaries of analytical development and quality control for safer and cleaner products especially in Gene and Cell Therapies
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  • On Demand Webinar

The Power of Partnership with Janssen – Advancing the Future of Cell and Gene Therapy Analysis

The Power of Partnership with Janssen – Advancing the Future of Cell and Gene Therapy Analysis
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  • On Demand Webinar

Smaller Particle and Low Adsorption Columns for Fast and Efficient Characterization of AAV through SEC-MALS

Smaller Particle and Low Adsorption Columns for Fast and Efficient Characterization of AAV through SEC-MALS
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  • On Demand Webinar

Advancing the Analysis of rAAV Viral Vectors using LC-MS Technologies

Advancing the Analysis of rAAV Viral Vectors using LC-MS Technologies
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  • Poster

Stability Characterization of Multiple Serotypes of Adeno-Associated Virus Using Charge Detection Mass Spectrometry

Stability Characterization of Multiple Serotypes of Adeno-Associated Virus Using Charge Detection Mass Spectrometry
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Learn more about Viral Vector Solutions.

Learn more about Viral Vector Solutions.
Characterize LNPs to ensure product safety and efficacy.
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