Advances in genetics and bioengineering have enabled the development of gene therapy and, with it, the unprecedented potential to treat diseases caused by recessive gene disorders, acquired genetic diseases and some viral infections.
Technologies for manufacturing and analysis of gene therapy products are evolving with continued efforts for full optimization.
Throughout this article, you will discover analytical solutions, from characterization through to control.
What are adeno-associated virus (AAV) vectors?
AAVs vectors are the most common viral vectors to deliver the healthy gene, due to their safety, low immunogenicity, and long-term transient expression.
The complexity of AAV gene therapy products
AAV based gene therapeutics are far more complex than many traditional biotherapeutics. Besides the full capsid containing the desired gene material, the final product could contain many different types of process and product related impurities.
Click here to download an infographic to learn more about analytical solutions to accelerate your AAV gene therapy.
To explore AAV gene therapy workflows, click here.
With the right analytical tools, scientists can expedite the development of safe, high-quality gene therapy products while reducing time to market and costs of manufacturing.
Empty/full capsid analysis
Empty capsids, which do not contain the gene therapy of interest, and partial capsids, those containing only a fragment of the gene of interest, are byproducts of the AAV production and can impact product safety and efficacy.
The amount of full, partial, and empty capsids, therefore, needs to be characterized and monitored through process development.
A native MS-based approach provides the necessary improvements in sensitivity and selectivity when compared to ultraviolet (UV) and fluorescence-based separation approaches, respectively.
Intact mass analysis
AAV capsid composition impacts viral infectivity and gene transduction. To ensure the safety and quality of gene therapies, AAV capsid and their constituent proteins need to be well characterized and monitored.
MS-based Intact mass analysis provides a robust and sensitive approach for capsid characterization. Mass confirmation can be performed with high confidence using the Thermo Scientific™ Q Exactive™ UHMR Hybrid Quadrupole-Orbitrap™ mass spectrometer.
Capsid protein characterization
It is important to understand the capsid identity because each AAV serotype has unique capsid proteins that transfer the genetic material to specific cells or organs.
Depending on the therapeutic target area, the correct AAV serotype is chosen and identified, then purity monitored. All AAV capsids consist of three proteins (VP1, VP2, and VP3) that share high-sequence homology. Ensuring the identity and purity of these proteins is critical to viral infectivity and viral transfer.
Host cell protein analysis
Host cell proteins (HCP) can impact quality or safety, or compromise product stability. Peptide analysis by LC-HRAM-MS offers orthogonal solutions for detection and monitoring of HCPs compared to immunological methods with the unbiased discovery of HCP impurities and subsequent quantitation.
HRAM (high resolution accurate mass) MS data combined with Thermo Scientific™
BioPharma Finder™ software provides comprehensive HCP qualitative and quantitative analysis.
When you partner with a company like Thermo Fisher Scientific, you will have access to expertise and an unparalleled product portfolio. This will allow you to accelerate the development of your gene therapy-based product(s) by utilizing flexible, robust, accurate, and scalable methods for product manufacturing, analytical testing, and characterization.
To learn more about gene therapy analytical solutions, download our NEW solutions guide by clicking the link here.
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