Rapid HSV Vector Iteration for a Gene Therapy Platform

Replay Bio, a biotech developing a herpes simplex virus (HSV) gene therapy platform for rare genetic diseases, needed a gene therapy CRO to deliver high-quality in vivo data fast enough to iterate on its HSV vectors and meet year-end funding milestones. HSV vectors carry up to 152,000 bases, far beyond the ~4.7 kilobase limit of AAV, but that scale makes them slow and complex to test. Melior Discovery built a customized in vivo model around Replay Bio’s HSV vectors and expedited key readouts, including a seven-day data point within a 30-day study. This fast HSV vector design-iteration cycle and a durability and efficacy data package gave investors confidence and moved the platform toward clinical readiness.

Gene therapy’s therapeutic reach is constrained in large part by how much genetic material a vector can carry. AAV, the workhorse of the field, is limited to a packaging capacity of roughly 4.7 kilobases, which puts many large genes and multi-component constructs out of reach. HSV-based vectors offer a fundamentally different envelope: the capacity to carry up to 152,000 bases, dramatically expanding the range of genetic diseases that a single therapeutic construct can address.

Replay Bio, co-founded by CEO Lachlan MacKinnon, is a biotech built around this opportunity: an HSV gene therapy platform aimed at rare genetic diseases. Realizing that potential, however, requires more than a promising vector. It requires rapid, reliable in vivo evidence that a given design expresses, persists, and performs as intended. Generating exactly that kind of evidence is the core function of a gene therapy CRO. Melior Discovery, drawing on decades of experience in animal model studies, in vivo phenotypic screening, and drug repositioning, partnered with Replay Bio to deliver it.

The scientific ambition of a 152,000-base vector comes with a matching operational burden: a construct that complex is difficult to design, build, and test quickly. Replay Bio’s core problem was velocity without loss of rigor. Specifically, the team needed to:

• Align sequence design, construction, and testing so that each could feed the next without stalling against tight deadlines.
• Receive rapid in vivo performance feedback, so that expression and delivery data could inform the next round of sequence refinement.
• Track vector expression over time to establish the durability that both the science and prospective investors would demand.

Layered on top was a funding dimension. Replay Bio needed a durability and efficacy data package in hand by year-end to demonstrate the platform’s viability to stakeholders. That made the timeline non-negotiable, and it made the choice of gene therapy CRO consequential. The partner needed to deliver not just speed, but the preclinical expertise, adaptability, and data quality that would hold up in front of investors.

Melior addressed the problem by building a model around Replay Bio’s platform rather than forcing the platform into a standard assay.

Customized in vivo model. Melior developed a preclinical model tailored to Replay Bio’s HSV vectors, designed to apply and precisely track vector expression over time. Its in vivo modeling expertise ensured the data generated mapped directly onto Replay Bio’s therapeutic goals rather than producing readouts that needed reinterpretation.

Scientific integration, not just execution. Unlike a transactional vendor, Melior collaborated closely with Replay Bio and drew on prior published research to shape experimental design. Melior’s scientists acted as a genuine thought partner in designing the experiment and reasoning through the study alongside the team rather than simply running instructions.

Comprehensive validation. Before the model informed any decision, Melior conducted validation testing to confirm its reliability and its ability to generate accurate data for optimizing therapeutic vectors.

Expedited, flexible data delivery. Melior accommodated evolving protocols and expedited specific readouts on request, most notably delivering a seven-day analysis inside a 30-day study, so Replay Bio could iterate on vector designs without waiting for full study completion.

The collaboration compressed Replay Bio’s iterative design cycle. Fast, directly relevant in vivo data let the team refine HSV vector designs more efficiently, reducing the time and resources such complex gene therapy work typically consumes, with key data points delivered within days.

Just as important, the resulting preclinical efficacy and durability data package gave Replay Bio a compelling, evidence-backed story for stakeholders. It allowed the team to demonstrate the durability of its gene therapy platform and make informed decisions at a moment when year-end timing mattered for funding.

Beyond the immediate deliverables, the partnership established a foundation for future studies and positioned Melior as an embedded, long-term gene therapy CRO partner in Replay Bio’s progress toward clinical readiness. As Martin summarized the working relationship, Melior felt like an extension of the team, invested in the platform’s success and communicating with the clarity of an in-house group.