In the rapidly developing field of gene therapy, Pace® is considered an experienced veteran. Since 2015 we have worked closely with our customer-partners to accelerate processes and provide support throughout the gene therapy product development cycle.

Biocompare, The Buyer’s Guide for Life Sciences Published an Article: The Changing Landscape of Gene Therapy, written by Frank Tagliaferri, Ph.D., VP of Pharmaceutical Development & GM at Pace® Life Sciences (PLS).

Project Commitment

Pace® scientists and project managers are committed to the success of your project. You will have access to experts who can offer advice and guidance based on similar work performed in our gene therapy labs. Our project managers also understand your need for us to be flexible in project scope and timing.

The work you do to improve lives is important to us, too. Part of our commitment to you is to understand your business so we can best advise you and anticipate your needs. We also know communication is important to you and lean toward over-communicating the status and timelines of our work on your behalf. If you have a need, reach out to consult with one of our gene therapy experts.

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Gene Therapy Development Pathway to Commercialization

Gene Therapy Research & Development

In early-phase gene therapy development, we work with you to determine the most reliable analytical methods to provide the data needed to guide effective development decisions. Next, we deliver a robust assessment of the physicochemical and biophysical characteristics of the therapeutic molecule. Often, this may include a sub-set of attributes: 

  • Determination of molecular weight (DNA / RNA) 
  • Conformation of nucleic acids
  • Thermal and chemical stability 
  • Determination of molar extinction coefficient 
  • Capsid integrity and protein composition 
  • Lipid Nanoparticle (LNP) composition and size distribution 
  • Encapsulation efficiency (LNP / VLP) 

Pace has supported the following molecule types:

  • Native and modified DNA (single- and double-stranded) mRNA, circRNA, tRNA 
  • Small interfering RNA (siRNA) 
  • O-methyl/locked nucleic acids (LNA) 
  • Peptidic nucleic acids (PNA) 
  • Phosphorodiamidate morpholino oligos (PMOs) 

Dedicated Analytical Strategies: Oligonucleotides

The term oligonucleotides includes a broad range of molecules with different chemical compositions and covering a variety of molecular weights, ranging between 15-20 nucleotides (e.g., siRNA) and many thousands of nucleotides (e.g., mRNA and DNA expressing whole genes). Additionally, nucleic acid-based API are commonly administered with a suitable delivery vehicle protecting them from the environment and enhancing or targeting their delivery to the cell type where action is required. Lipid nanoparticles (LNPs) and virus like particles (VLPs) are common delivery methods.

The recent introduction of novel genome editing technology such as CRISPR/Cas9 has further expanded the complexity of the nucleic acid repertoire and innovative gene therapy platforms posing new analytical challenges are likely to emerge. With this complexity in mind and leveraging our experience in all the platforms described, Pace® develops dedicated analytical strategies for each specific project. View more information on oligonucleotides.

On-Demand Webinar: Integrated CMC Development of Gene Therapies

Gene Therapy Development Services

Establishing a robust process for gene therapy drug production enables pre-clinical development and ultimately, formulation development for clinical trial materials. To support this process, specific strategies need to be developed for:

  • Secondary structure assessment and sizing
  • Oligomeric state of nucleic acid particles in solution
  • Purity analysis and quantitative detection of primary components
  • Degradation products in raw materials
  • Process samples and final drug substances

Optimal drug product composition is then formulated within a range of boundary conditions informed through the process development activities. Vehicles, including liquid solution or suspension, lipid nanoparticles, and virus-like particles allow options for administration, such as intravenous (IV), subcutaneous, or inhalation delivery. When long-term stability in an aqueous buffer is not possible, lyophilization of oligos enables storage at ambient conditions and simplifies preparation of the administrable dosage form.

A final significant consideration is the bioanalytical evaluation of preclinical and clinical samples. While FDA regulatory guidelines are not specific for oligonucleotide drugs, these substances are often treated as small molecules due to the synthetic manufacturing processes used in their production, despite their large size and biochemical properties. Methods to determine the fate of the molecular entity, metabolites, and the unique delivery vehicles is a frequent consideration to satisfy regulators.

Gene Therapy Analytical Support Services

Pace Analtical Oakdale LaboratoryPace® provides full-service, extensive analysis capabilities for gene therapies leveraging analytical methods, physicochemical, biophysical, and/or biopharmaceutical characterization. The deep experience of the Pace team coupled with our cutting-edge FDA-approved GMP facilities allows us to provide analytical support your novel gene therapies through manufacturing and commercialization. Learn more about Pace® GMP testing laboratories.