Rethinking Rare Disease: Why gene therapy must be built backwards to succeed

In the race to deliver gene therapies for rare diseases, many promising programs fail not because of flawed science, but because they weren’t designed with all the nuance required for success in today’s tightly funded and competitive market. Many therapies, often emerging from brilliant academic labs or mission-driven startups, frequently collapse under the weight of downstream challenges, including regulatory delays, manufacturing bottlenecks, and misaligned commercial strategies.

ViroCell Biologics proposes a more effective approach. In their thought-provoking framework, Drs. Nicholas Ostrout and Farzin Farzaneh urge developers to “build backwards,” starting every rare disease gene therapy program with the end in mind.

This approach reshapes the industry’s perspective on innovation: not merely as discovery, but as a disciplined design that aligns with the clinical, regulatory, and commercial endpoints ultimately determining whether a therapy reaches patients.

Why Rare Disease Demands a New Development Model

Rare disease programs operate under unique pressures, including small, dispersed patient populations, limited funding, and often a lack of clear commercial pathways. The traditional linear discovery model, followed by preclinical safety/tox studies, and then clinical trials, frequently fails due to lack of funding and/or time. Decisions made too late in development can become costly, if not fatal.

Instead, “building backwards” asks developers to define success upfront. What clinical outcomes are necessary for real-world adoption? What manufacturing realities must be considered early on? How can we reduce costly animal studies? What regulatory expectations must the data meet?

When these endpoint considerations guide development decisions from vector design to dosing strategy, the result is a program that is not only scientifically sound but also engineered to reach the clinic, earn approval, and deliver long-term patient access.

The Power of Early, Unified Collaboration

In rare diseases, early misalignment can derail even the most promising therapies. That’s why building backward also means building together. The best programs bring together scientists, contract development and manufacturing organizations (CDMOs), regulatory experts, and patient advocates from the start.

By aligning with stakeholders early, teams can choose the right vectors, design feasible manufacturing protocols, and create regulatory narratives that anticipate reviewer questions. This multidisciplinary integration is no longer optional; it is essential to avoid rework, delays, and unnecessary risk.

Designing for a Platform

ViroCell highlights the strategic importance of platform-based development for rare diseases. Rather than creating custom vectors for each new indication, developers can utilize modular backbones that accommodate multiple related conditions.

ViroCell’s modular lentiviral system enables developers to swap in promoters, genes of interest, and targeting ligands without having to start from scratch. This approach lowers costs, streamlines regulatory efforts, and facilitates faster scaling across rare disease families.

By building backwards, platform thinking becomes not just efficient, it becomes inevitable.

Precision Through Genetic Screening

One caution with platform approaches: disease groupings must be validated through robust genetic screening. Too often, conditions are categorized by symptom rather than mechanism. Without a precise understanding of disease biology, platforms can misfire.

ViroCell stresses that genomic clarity is foundational to any strategy aiming to reuse vectors, delivery routes, or manufacturing workflows. It’s not just science, it’s strategic infrastructure.

Regulatory Success Starts at the Design Table

Regulatory reviewers don’t just assess data; they interpret stories. Why was this design chosen? How does it mitigate risk? What’s the rationale behind the delivery strategy?

Building backwards involves creating the story from the beginning. It requires writing a coherent narrative that connects each design choice to a clinical need or safety consideration.

ViroCell actively supports clients in developing regulator-ready programs by incorporating regulatory logic into vector design and manufacturing decisions, rather than considering it an afterthought.

Rethinking Licensing for Academic Innovation

Even the best rare disease programs can stall at the first hurdle: licensing. When universities or research centers apply big-pharma deal structures to ultra-rare indications, innovation dies on the vine.

ViroCell promotes more flexible licensing models that correspond with the risk and reward profile of rare diseases. Deferred royalties, non-exclusive rights, and milestone adjustments can all support the development of therapies.

It’s not about giving value away; it’s about enabling value to be realized.

Toward a Shared Industry Playbook

The final call to action is a collective one: as the field expands, rare disease gene therapy requires reusable frameworks. From toxicology templates, to alternative or alternate animal models, to regulatory roadmaps, a shared playbook can minimize duplication and democratize the development process.

Initiatives such as the Bespoke Gene Therapy Consortium are leading the way. However, increasing open knowledge sharing, particularly from experienced CDMOs like ViroCell, will be crucial for developing scalable and sustainable systems.

Build to Deliver

The message is clear: rare disease gene therapy isn’t just a scientific challenge; it’s a systems challenge. To succeed, developers must start at the finish line. Define success. Align early. Design with intention. Then, build every step to serve that vision.

For the patients waiting and the science ready to help them, we must stop building forward in hope.

We must build backwards with purpose.