For patients with rare genetic diseases and cancer, gene therapy ex vivo treatments often require extracting cells, engineering them in a lab, and reinfusing them into the patient - a process that can take weeks and cost hundreds of thousands of dollars per patient. In vivo delivery offers a different approach, administering the therapeutic vector directly to the patient and reprogramming cells in place. The results thus far have been impressive with sponsors reporting cost reductions approaching tenfold per patient, and the pipeline of in vivo programs is expanding quickly. Large pharma is taking notice: Eli Lilly recently agreed to pay up to $7 billion to acquire Kelonia Therapeutics, a developer of an in vivo lentiviral CAR-T platform, following early clinical data showing rapid, deep responses in multiple myeloma patients.

Since Ampersand’s investment in VIVEbiotech, a CDMO focused exclusively on lentiviral vector development and manufacturing for cell and gene therapy, VIVEbiotech has built on its position as one of the few CDMOs in the world authorized to release GMP-grade lentiviral vectors as final drug products. With 15 in vivo programs in its portfolio, several already FDA-cleared for clinical trials, VIVEbiotech sits at the center of one of the most consequential shifts in modern medicine. We sat down with CEO Jon Alberdi and CTO Marie Fertin to discuss what’s driving the in vivo shift, how VIVE is positioned to lead, and what sponsors need to know.

The CGT space has been dominated by ex vivo approaches for years. What factors are driving the industry's growing interest in in vivo cell and gene therapies?

(Jon Alberdi): Ex vivo has delivered transformative outcomes, but it carries real challenges such as manufacturing complexity, cost, logistics, and patient access. In vivo removes many of those steps by engineering cells directly inside the patient, simplifying logistics and cutting cost; sponsors are quantifying almost a tenfold decrease in cost per patient for some therapies. VIVEbiotech has worked in in vivo for close to a decade and today runs 15 in vivo programs, likely more than any other CDMO in the space, with interest growing across both emerging biotechs and large pharma.

Where do you see in vivo lentiviral vectors having the most transformative near-term impact - CAR-T, rare diseases, gene editing, or another area?

(Jon Alberdi): Most immediately in cell engineering - CAR-T and immune cell reprogramming, and in rare diseases, where long-term gene expression favors lentiviral vectors. Further ahead, we expect this to combine with gene editing, where targeted delivery will be critical.

(Marie Fertin): The different vector technologies aren't direct competitors as each suits different needs, whether transient or permanent expression, or RNA versus DNA cargo. Lentiviral vectors, originally engineered for ex vivo, have changed the game in recent years by moving into in vivo through vector engineering developed specifically for that use.

What are sponsors looking for in a manufacturing partner as they transition from ex vivo to in vivo programs? How are those expectations changing?

(Jon Alberdi): Sponsors are becoming significantly more demanding, because in in vivo the vector is the drug product itself, administered directly to the patient, raising the bar on quality and purity. Our development team has achieved up to a threefold improvement in purity levels compared to ex vivo. Beyond that, sponsors weigh experience, manufacturing scale, and regulatory knowledge, and increasingly want to collaborate with a partner early to align on quality and regulatory strategy.

What should sponsors be doing now to set their in vivo programs up for long-term success, particularly when it comes to selecting partners and planning for scale?

(Marie Fertin): In vivo lentiviral vector-based therapy is still a new field, so choosing a CDMO with deep, specialized knowledge of this specific vector (including its therapeutic modes of action) is important. Partnering with a CDMO that's already running multiple in vivo programs is a genuine de-risking decision, both technically and regulatorily.

In vivo lentiviral vectors come with more stringent manufacturing requirements than ex vivo applications. What capabilities should sponsors look for in a CDMO, and why are they so important?

(Marie Fertin): A key hurdle is the change in envelope (moving from the VSV-G tropism typical of ex vivo vectors to one that targets specific cell types), which can significantly affect the manufacturing process and product quality attributes. Our track record lets us address that early, at small scale and lower cost, building specific knowledge for each in vivo vector so programs reach the clinic without issues.

(Jon Alberdi): Regulatory experience matters too. Across our 15 programs, several already in the clinic, the constant feedback we get from agencies while supporting sponsors' dossiers is a real differentiator.

As more in vivo programs enter the clinic, how are regulatory expectations around manufacturing evolving, and what should developers be doing now to stay ahead of those requirements?

(Marie Fertin): The core difference is that the viral vector is now the final product administered to the patient, not just a tool for modifying cells beforehand. That raises the criticality of every quality attribute, since each bears directly on patient safety and efficacy. Regulators expect correspondingly stringent control of the manufacturing process throughout the supply chain.

Looking ahead, what do you think the in vivo cell and gene therapy landscape will look like over the next five years? What trends do you expect will shape the next wave of innovation and commercialization?

(Jon Alberdi): The next five years will mark the transition of in vivo therapies from a promising concept to a clinically validated, increasingly commercial reality, as advances in targeting technologies, vector engineering, and manufacturing improve safety, efficacy, and scalability. That said, ex vivo isn't going anywhere; the two will coexist depending on the therapy, scale, and purpose.

An Evening of Networking at BIO San Diego

More than 250 guests joined Ampersand and its portfolio companies for an evening of networking at the Altitude Roof Deck overlooking PETCO Park during BIO 2026 in San Diego with a Padres win as the backdrop. The evening brought together industry leaders, clients, and partners from across the life sciences ecosystem, including representatives from our portfolio companies Alcami, Avid Bioservices, BIOLOGOS, Biosynth, CurTec, Gannet BioChem, Genezen, NanoImaging Services, Phosphorex, ProtaGene, Resolian, Tjoapack, and VIVEbiotech. Thank you to everyone who joined us - the conversations and connections will carry on in the months ahead.