Cell and gene therapies (CGTs) are reshaping medicine with the promise of one-time, potentially curative treatments. Yet the path from lab to patient is paved with challenges. Manufacturing remains a major constraint, regulatory frameworks are evolving, and the economics of access are still being tested.

At AVANT, our perspective is shaped by both history and conviction. We saw how bioprocessing once embraced single-use technologies – not as a minor efficiency gain, but as a paradigm shift that changed the entire industry. Today, we believe cell and gene therapies demand that same kind of quantum leap, as Daniella Kranjac, Founding GP at AVANT BIO puts it: 

“Incremental fixes aren’t enough. If you’re using yesterday’s tools to solve today’s problems, you’ll never catch up. We need quantum shifts.”

With this and an investor mindset, we look at the field through two lenses:

1. Where the science is breaking new ground.
2. Where that science becomes investable and scalable.

We also focus squarely on the early stages of the therapeutic pipeline, discovery, preclinical development, and scale-up. Too often, these steps are rushed or overlooked in the race to produce clinical material. But if innovation doesn’t happen here, inefficiencies cascade downstream. That’s why we prioritize and seek out investments in advanced AI/ML platforms, digital twins, and other disruptive technologies that not only accelerate discovery but also introduce the robustness and simplicity needed to meet regulatory expectations.

Market and Regulatory Landscape

The fallout from the ELEVIDYS case has reset the conversation around risk and benefit. Regulators are reminding the field that speed matters, but safety is paramount.

Regulators are also recalibrating the balance between accelerated approvals and confirmatory evidence. Longer timelines create opportunities for CDMOs and CMC innovators to shine through with more robust data packages and better comparability tools.

Meanwhile, global divergence in CMC and quality expectations continues to complicate international programs. Digital platforms that harmonize data packages across regions and reduce regulatory friction rather than add to it will be essential.

Manufacturing Capacity and Modalities

Vector capacity remains the most visible bottleneck, particularly for AAV and lentivirus. Yet as Daniella notes:

“The bigger issue is that we’re trying to scale therapies with yesterday’s tools. We need innovative new platform approaches with smarter analytics to really move the needle”

Non-viral systems like lipid nanoparticles (LNPs) and polymeric carriers are diversifying the delivery toolbox, though they still require new formulation and QC solutions.

DNA substrates are also evolving. Synthetic and enzymatic DNA are poised to replace plasmid DNA by offering faster, cheaper, and more resilient supply chains – shaving months off development timelines.

In cell therapies, autologous approaches remain viable in the near term, but allogeneic platforms represent the scalable long-term path. Here, closed, automated systems are the unlock for reliability at population scale. Looking even further ahead, in vivo reprogramming could redefine manufacturing altogether, but the regulatory and logistical frameworks are not yet ready.

We’re also looking at technology disruptors like AI/ML, and digital twins which are no longer in their infancy stage, they’re at the core of the next paradigm. These tools are becoming smart ways to test before you fail, to bend timelines without breaking quality.

AVANT BIO prioritizes innovation that multiplies efficiency rather than incrementally nudging it forward.

CMC, Analytics, and Comparability

Potency assays are still the Achilles’ heel of advanced therapy development. Without alignment to mechanism of action, programs risk proceeding without real insight into efficacy.

Real-time release is another frontier. AI, digital twins, and process analytical technologies are enabling developers to “fail fast” and release product faster, but only if they simplify QC, not overcomplicate it.

Comparability, particularly when process or vector changes are introduced, remains one of the greatest risks. Closed, harmonized systems and standardized assays can mitigate these pitfalls.

Supply Chain, Policy, and Geopolitics

Critical raw materials remain fragile links in the supply chain – If your capsids or lipids come from one vendor, you don’t have a supply chain – you have a single point of failure.

Reshoring and dual sourcing are costly, but geopolitical shifts such as the BIOSECURE Act are forcing companies to rethink sourcing. Synthetic alternatives and new domestic suppliers will play a critical role in the next generation of resilience strategies.

Clinical Operations Interface

For autologous therapies, vein-to-vein orchestration is often the bottleneck. Digital scheduling platforms act like air-traffic control, keeping the system from collapsing under its own complexity.

Chain of custody and cryochain reliability are equally critical. Decentralized, closed-system processing could reduce risk and increase resilience. In vivo approaches will eventually reshape logistics entirely—but not without significant regulatory groundwork.

Collaboration and Ecosystem Models

Co-development partnerships between innovators and CDMOs are proving most effective, aligning incentives around speed and quality. Contracting models are also evolving. Risk-sharing and outcomes-based agreements are inevitable, requiring lifecycle evidence planning from day one. Rare-disease indications will remain a focus, but scalable platforms will be the key to expanding into larger populations.

Precompetitive consortia are also important, setting standards for assays and reference materials that reduce redundancy across the industry.

Conclusion

Cell and gene therapies hold extraordinary promise, but their future depends on more than scientific breakthroughs. They require enabling tools, technologies, and services that deliver true paradigm shifts, transformations as disruptive as single-use technologies were in their day.

At AVANT BIO, we are committed to backing innovators who can deliver those quantum leaps. By focusing on early stages of the pipeline, supporting breakthrough platforms like AI/ML and digital twins, and championing scalable, sustainable manufacturing, we aim to accelerate the next generation of cures—and ensure they reach patients worldwide.