Navigating Gene Therapy Development

In April 2026, the FDA approved the first gene therapy for genetic hearing loss, Otarmeni, setting a record for the fastest Biologics License Application (BLA) approval in history. This feat is a testament to the evolution of gene therapies from a narrow definition – delivery of a functional gene using viral vectors to replace a missing or non-functional gene – to a technologically diverse and relatively safer therapeutic class, including AAV-based therapies (Otarmeni), antisense oligos (ASOs), siRNA, mRNA vaccines, and other viral vectors (e.g. adenovirus, lentivirus, etc.).

While each therapeutic modality works differently, all must translate sophisticated biology into a product that is safe, reproducible, and practical to manufacture. In the blog that follows, we cover a few key considerations for preclinical gene therapy developers as they work toward clinical development and commercialization.

#1: Consider Safety and Immunogenicity Characterization Early

Viral vectors, in particular adenovirus, have a long and checkered history of safety concerns. From the infamous 1999 death of Jesse Gelsinger to the recent deaths from unapproved AAV-based gene therapies, safety issues due to overblown immune responses to gene therapies are well known but not always documented.

Whether developing a nucleic acid therapeutic or viral vector, developers must ask relevant questions about a gene therapy’s innate and adaptive immune responses, pre-existing immunity, oncogenicity risk, biodistribution, off-target transduction and, for integrating vectors or genome editing platforms, unintended genomic changes, whether temporary or permanent. Addressing these risks early can inform candidate selection and prevent late-stage redesign.

#2: Assess Product Quality and Impact on Efficacy and Safety

For AAV products, particle size, aggregation, capsid titer, full-to-empty capsid ratio, and nucleic acid content can influence consistency and potency. These physical and molecular characteristics can affect the effective dose administered to patients. A high proportion of empty or partially-filled capsids, for instance, can dilute the effective dose while still exposing patients to capsid proteins, which can cause safety issues.

Nucleic acid therapeutics bring their own concerns, including integrity, stability, and delivery-system performance.

Analytical characterization should therefore develop alongside functional assays, not after selecting a lead candidate. A product may meet basic concentration or purity measurements yet perform poorly in cell-based assays. Conversely, a potent early candidate may prove difficult to manufacture consistently. Evaluating quality and function together helps identify these discrepancies before substantial resources are committed to a lead candidate.

#3: Anticipate Scale and Regulatory Expectations

Laboratory-scale performance does not guarantee comparable results as production expands to commercialization. Changes in raw materials and production or purification conditions can affect yield, aggregation, and potency. Storage and transportation introduce further risks, including temperature excursions, freeze-thaw cycles, and agitation. Early stability and stress testing can help establish suitable formulations, storage conditions, and shipping procedures.

Analytical methods must also be validated across batches, operators, and testing sites. Defining critical quality attributes (CQAs) early and linking them to biological activity and safety helps sponsors evaluate comparability following process changes, facilitate technology transfer, and provide regulators with clear evidence that the scaled product continues to perform as intended.

Eurofins Discovery: Integrated Support for Gene Therapy Programs

Eurofins Discovery supports early gene therapy programs, including nucleic acid therapeutics and viral vectors, in building a strategic path from early R&D toward IND approval. For AAV-based therapeutic programs, defined workflows cover vector design, production, purification, characterization, and delivery to help sponsors evaluate safety, function, and consistency.

Our combination of established workflows and scientific expertise helps to address development and scalability challenges earlier. Support can extend from discovery through manufacturing, including assay and protocol transfer to qualified teams across the broader integrated Eurofins Discovery network, creating greater continuity as programs advance toward the clinic.

Contact us to learn more about our gene therapy development capabilities and how to avoid common barriers to clinical development and commercialization.

Navigating Gene Therapy Development

#1: Consider Safety and Immunogenicity Characterization Early

#2: Assess Product Quality and Impact on Efficacy and Safety

#3: Anticipate Scale and Regulatory Expectations

Eurofins Discovery: Integrated Support for Gene Therapy Programs

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