Gene therapy development

The use of viruses as cell and gene therapy vectors is complex, and in this fast-moving field there is no playbook to help you develop methods and safely scale-up products and processes.  

Do you recognize these challenges?

• Establishing a fit-for-purpose analytical toolset to identify and validate the critical quality attributes of complex proteins
• Identifying and implementing appropriate methods that generate the data needed to ensure the safety, potency, and purity of viral vectors
• Keeping up to date with the latest technology and approaches, while quickly repurposing existing tools and processes 
• Staying compliant with constantly evolving regulatory guidelines that vary from country to country
• Finding the efficiencies, people, and resources to develop innovative products and processes 
• Overcoming the hurdles associated with complex tasks, such as capsid design, quality control and process optimization 
• Successfully transferring new discoveries to scale-up and manufacturing

Malvern Panalytical provides more than world-leading instrumentation. 

Developing viral vectors requires fit-for-purpose tools and the know-how to apply them to generate the data you need. With years of experience supporting customers in the development of gene therapy products, our application scientists have the knowledge to help you access breakthrough insights from your analytical toolbox.

Work with us to overcome your gene therapy challenges: 

• Utilize fit-for-purpose analytical instrumentation that identifies multiple critical quality attributes and delivers efficient and compliant methods
• Discover tools to characterize viral titer, empty/full ratio, aggregation content and batch-to-batch consistency via an orthogonal approach to analytics across multiple vectors
• Quickly realize the full value of your investment in analytical technology with training and support for your team
• With unrivaled experience in the use of advanced instrumentation for gene therapy applications, our scientists can act as a flexible extension to your team
• We provide method development services to overcome your specific challenges
• We help you develop reliable, repeatable techniques that improve the efficiency of your workflows 

We’re ready to apply a combination of analytical instrumentation and years of experience to provide flexible support, wherever and whenever you need it – to drive forward the therapies of the future.

Whatever characterization challenges you are facing, chances are we’ve worked with a team just like yours and helped them implement the technology and methods needed to make safe and effective drug products faster. 

To find out how our team of experts can accelerate the development of your next product and speed up your journey to market, contact us today.  

From capsid design, through the optimization of downstream process conditions, to formulation and stability tests and the extended characterization of drug substances and drug products, technologies such as Dynamic Light Scattering (DLS), Electrophoretic Light Scattering (ELS), Multi-Angle Dynamic Light Scattering (MADLS), Size Exclusion Chromatography-Multi-Angle Light Scattering (SEC-MALS), Nanoparticle Tracking Analysis (NTA), Grating-Coupled Interferometry (GCI), Isothermal Titration Calorimetry (ITC) and Differential Scanning Calorimetry (DSC) are used to inform scientists on the key analytical and quality attributes of viral vectors, enabling characterization, comparison and optimization of:

• Capsid size (DLS, SEC, NTA)
• Capsid titer or particle count (MADLS, SEC, NTA)
• Percentage of genome-containing virus particles / % full analysis (SEC) 
• Aggregate formation (DLS, MADLS, SEC, NTA)
• Fragmentation (SEC)
• Thermal stability (DLS, DSC)
• Higher-order structure analysis (DSC)
• Serotype identification (DSC)
• Capsid uncoating and genome ejection (DLS and DSC)
• Binding to receptor (ITC and GCI)
• Charge (ELS)

DLS, MADLS, SEC-MALS, NTA, GCI, ITC, and DSC are label-free quantification techniques which require minimal assay development and can be readily applied at all stages, strengthening the analytical workflow for gene therapy development.

Although the discovery process for gene therapy is shorter than that typically seen in traditional drug discovery, the high degree of product complexity introduces additional challenges which must be addressed early-on to assure the delivery of safe and efficacious products. Amongst these challenges are:

• Selection of a viral capsid based on optimal properties and function
• Rational protein engineering to improve and modify the properties and functionalities of the original viral capsid

The solutions in both cases are based upon a comprehensive set of physicochemical, biochemical, and biological data which informs on the performance of the viral vector and feeds back on the selection process. 

At this stage, extensive biophysical characterization of engineered capsids and viral vectors using DLS, MADLS, SEC-MALS, ITC, and DSC supports the reliable evaluation of important quality metrics and interpretation of the results of biochemical and biological assays, via measurements of capsid size and titer, aggregate formation, % full measurement, receptor binding, thermal stability and capsid uncoating propensity.