Ex Vivo vs In Vivo: The Big Shift Pharma is Betting On

A Pivotal Moment in Advanced Therapies

The life sciences sector is experiencing a transformative moment. The rise of cell and gene therapies (CGTs) has taken us beyond the era of small molecules and biologics into a new frontier where diseases can be treated - and in some cases cured - at the genetic level. Yet, behind the headlines of scientific breakthroughs lies a crucial strategic choice shaping the future of drug development: ex vivo vs. in vivo therapies.

Pharma’s growing interest in this dichotomy reflects more than just a technological shift. It signals a deeper rethinking of therapeutic delivery models, manufacturing scalability, and commercial viability. As advanced therapies move from rare disease pipelines toward mainstream indications, the industry’s strategic bets today will define the therapies (and the winners) of tomorrow.

 

Defining the Two Approaches

Ex Vivo Therapies: Precision Outside the Body

Ex vivo approaches involve extracting patient cells, modifying or engineering them outside the body (often with viral or gene-editing tools) and then reinfusing them into the patient. Perhaps the most well-known example is CAR-T cell therapy, where T-cells are engineered to target cancer cells with remarkable precision.

The scientific and operational advantages include:

• Controlled editing environment with robust safety checks before reinfusion.
• High precision in ensuring the right genetic modifications are made.
• Early regulatory comfort, as seen with several FDA-approved CAR-T therapies.

However, challenges do remain. The logistics of cell collection, modification, and reinfusion – which is often unique to each patient - make scaling complex and expensive. The “vein-to-vein” model demands highly specialised infrastructure, strict chain-of-custody protocols, and coordinated scheduling across clinical, manufacturing, and regulatory teams. As a result, the costs and timelines associated with ex vivo therapies remain a major barrier to scalability and broad patient access.

 

In Vivo Therapies: Editing Within the Body

In contrast, in vivo therapies deliver the therapeutic payload, whether it’s gene-editing machinery, mRNA, or viral vectors - directly into the patient’s body, enabling cells to be modified in situ.

Emerging platforms like AAV vectors, lipid nanoparticles (LNPs), and next-gen CRISPR systems have made in vivo approaches increasingly feasible.

Key benefits include:

• Potential for one-time, off-the-shelf treatments rather than bespoke manufacturing.
• Broader applicability across multiple tissue types and disease indications.
• Reduced manufacturing complexity and lower cost barriers as technologies mature.

With in vivo platforms, pharmaceutical companies can envision a future where genetic and cellular therapies are delivered much like vaccines or monoclonal antibodies today - produced at scale, distributed globally, and administered in a single visit. This scalability is critical not only for expanding access but also for making advanced therapies commercially viable in large, competitive therapeutic markets such as cardiovascular disease, neurology, and metabolic disorders. In vivo delivery is the path toward true scalability - bringing advanced therapies to larger patient populations beyond rare or ultra-rare diseases.

 

Ex Vivo to In Vivo: The Scientific and Strategic Drivers Behind the Shift

1. Manufacturing Bottlenecks and Commercial Scale

Pharma’s pivot toward in vivo modalities is partly driven by the manufacturing constraints of ex vivo therapies. Current ex vivo processes rely on specialised facilities, cold chain logistics, and highly skilled operators - all contributing to costs exceeding $400,000 per patient for some therapies.

In vivo delivery promises a standardised manufacturing process, akin to traditional biologics, with potential for mass production and global distribution. This scalability is key for pharma companies aiming to expand beyond niche indications into common conditions such as cardiovascular disease or diabetes, where patient populations number in the millions.

 

2. Delivery Science Breakthroughs

Early gene therapy efforts struggled with targeted delivery and immune system reactions. Today, innovations such as:

• Tissue-specific promoters for precision targeting
• Transient expression systems to mitigate long-term risk
• Next-gen CRISPR nucleases for higher editing fidelity

 - are rapidly addressing these concerns.

The success of mRNA COVID-19 vaccines has further validated LNP-based delivery systems, accelerating investment into in vivo platforms that can safely and efficiently deliver genetic payloads at scale.

 

3. Regulatory Confidence and Risk Profiles

Ex vivo therapies benefitted from early regulatory acceptance due to their controlled, lab-based processes. In vivo approaches, initially seen as riskier, are gaining favour as clinical data accumulates and long-term safety profiles improve.

The FDA’s recent approvals of in vivo gene therapies for conditions like haemophilia underscore a growing comfort level. Agencies now provide clearer guidance on vector safety, immunogenicity, and long-term follow-up, reducing barriers for pharma investment.

 

Investment Landscape: Pharma’s Multi-Billion-Dollar Bet

Pharma companies are investing heavily in in vivo technology platforms, with recent acquisitions and partnerships exceeding $10 billion globally in the past three years.

Notable deals include:

• Pfizer’s acquisition of Bamboo Therapeutics for AAV gene therapy platforms.
• Novartis’ expansion into in vivo editing through CRISPR collaborations.
• Vertex and CRISPR Therapeutics’ partnership for gene-editing therapies beyond rare diseases.

This wave of investment reflects confidence that in vivo delivery will unlock broader therapeutic markets, reduce cost of goods sold (COGS), and enable global scale-up.

 

HRS Perspective: Talent and Leadership for the Next Frontier

At HRS, we're seeing first-hand how this technological shift is reshaping talent requirements across the life sciences sector. Delivering next-gen therapies demands cross-functional expertise in:

• Genomic medicine and molecular biology
• Advanced biomanufacturing and automation
• Regulatory strategy for novel modalities
• Commercial leadership for global launches

Pharma companies are increasingly seeking executives who can integrate science, operations, and strategy - leaders capable of driving innovation while navigating evolving regulatory and commercial landscapes.

We believe the right talent is what transforms advanced therapies from concepts into cures, which is why we care so deeply about this space. We're continuing to partner with organisations to identify and develop this next wave of biotech leadership, ensuring that scientific breakthroughs translate into real-world and life changing patient impact.  

 

Toward a Hybrid Future

The debate between ex vivo and in vivo therapies is not a zero-sum game. Instead, the future likely lies in a hybrid therapeutic ecosystem, where each modality serves specific diseases, patient populations, and clinical contexts.

Pharma’s investment shift toward in vivo reflects its scalability, cost efficiency, and broad applicability. Yet, ex vivo therapies will remain essential for certain oncology indications and ultra-precise genetic interventions.

For biotech executives and investors, the message is clear: success in this evolving landscape will hinge on scientific innovation, strategic leadership, and organisational agility. Those who align talent, technology, and capital effectively - will define the next era of advanced therapies.