From The Editor | June 15, 2026

In Vivo Gene Editing Is Moving From Promise To Proof

Erin

By Erin Harris, Editor-In-Chief, Cell & Gene
Follow Me On Twitter @ErinHarris_1

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The cell and gene therapy field is increasingly focused on in vivo approaches as a critical direction for the next phase of the industry. Yet a key challenge remains. How do we move from isolated technical breakthroughs to therapies that are safe, durable, and scalable across patients and diseases? Delivery, durability, specificity, and manufacturability are now the defining constraints and differentiators for CGT.

That is why I launched this special in vivo series for Cell & Gene: The Podcast now. I believe the field has reached a true inflection point. The conversation is no longer just about what might be possible. It is about what is beginning to work in patients, where the real bottlenecks are, and which platforms are built to scale. Across Precision Biosciences, Beam Therapeutics, and Ascidian Therapeutics, the common thread is a shift from technical promise to clinical execution. This matters because in vivo approaches are no longer a side conversation. They are becoming a central test of whether the field can turn scientific ingenuity into real, repeatable patient impact.

“It’s very exciting to see clinical stage programs move into later phase development,” said Cassie Gorsuch, Ph.D., CSO at Precision Biosciences. Her observation reflects a broader maturation across gene editing, where the focus is no longer solely on what can be edited, but on what can be delivered safely and repeatably in patients. For CGT stakeholders, this signals a move away from isolated technical proof points and toward medicines that must survive regulatory scrutiny, scale-up demands, and long-term follow-up.

Delivery Still Defines the Field

If there is one bottleneck that surfaced repeatedly during all three episodes, it is delivery. “One of the big challenges that I think still persists is on the delivery side,” Dr. Gorsuch said. She added that options are limited outside the liver and noted that for indications such as Duchenne muscular dystrophy (DMD), AAV remains the practical choice even with its limitations. Her comments underscore a central reality for in vivo CGT, which is that scientific elegance does not matter unless the payload reaches the right tissue in the right form.

Beam Therapeutics’ CSO, Gopi Shanker, Ph.D. made a related point from a different angle, emphasizing why the company leaned hard into LNPs and targeted LNPs. He explained that Beam’s early decision to invest in LNPs was driven by concerns with the viral vectors and the need to expand beyond the liver. He then described targeted LNPs as a way to redirect that LNP away from the liver and to the cell type of choice. Taken together, these interviews show that delivery innovation is no longer ancillary to in vivo drug development; it is the core platform strategy.

Safety and Specificity Matter More Than Ever

The discussions also made clear that in vivo therapies are being judged on more than efficacy. Dr. Gorsuch stressed that specificity is certainly a top priority for any gene editing company and described Precision’s comprehensive package for identifying, confirming, and assessing the functional consequences of off-target sites. That emphasis reflects a field-wide expectation that regulators and developers now want not just a map of where edits may occur, but an understanding of what those edits do.

Dr. Shanker’s explanation of base editing reinforced why many teams are pursuing alternatives to double-strand break approaches. He said base editing avoids those breaks and leads to consistent and highly predictable outcomes. He also noted that the process is gentler on the cells, since the DNA damage response is not activated in the same way. For the CGT sector, that combination of predictability and lower cellular stress is especially important in systemic in vivo settings, where tolerability can make or break a program.

Platform Design Is Becoming More Strategic

Another clear theme demonstrated throughout the series is that platform design is becoming more intentional. Dr. Gorsuch said Precision is a believer in knowing your technology well and applying it where it can really shine. That philosophy helps explain why the company is applying ARCUS nucleases differently across hepatitis B and DMD, using the platform’s small size and unique cut profile to fit the biology of each disease. The episode suggests that the next generation of CGT winners may be those that resist one-size-fits-all thinking.

Ascidian Therapeutics’ Founder, President, and CEO, Michael Ehlers, M.D., Ph.D., made a similar argument from the RNA side. He said tissue specificity is foundational but also a big strategic constraint across the field and added that long-term success depends on expanding beyond those comfort zones. His framing is useful because it broadens the definition of platform value: the winning approaches will not only edit effectively, but will do so across tissues, exposure levels, and use cases without constant reinvention. That is a high bar, but one the field increasingly seems willing to meet.

Regulatory Flexibility Is Opening Doors

All three episodes also show a more pragmatic regulatory environment taking shape. Dr. Shanker described Beam’s alignment with FDA on an accelerated approval pathway as something built on biomarkers that were built into the program right from the get-go. He suggested this kind of evidence-based flexibility may become the standard for therapies that address the root cause of disease. That is especially relevant for CGT companies developing programs in rare disease or serious chronic disease settings, where conventional clinical endpoints may be slow or hard to measure.

Dr. Gorsuch similarly pointed to the importance of aligning early with regulators on specificity and safety packages and shared that FDA’s draft guidance on off-target analysis was very much in line with what they’ve already assembled. This kind of convergence between developer strategy and regulator expectation can shorten the path to clinic and de-risk later-stage development.

What Comes Next for CGT

The biggest takeaway from the series is that in vivo CGT is entering a new phase, which is defined less by conceptual promise and more by reproducibility. Dr. Ehlers said the field needs precision, durability, and predictability, and argued that the next leap requires a shift from heroic single programs to reproducible pipelines. That line may be the best summary of where the sector stands today.

Across the three episodes, the message is consistent: in vivo is becoming one of CGT’s most important test cases. The companies highlighted in the series are not only chasing firsts but also building the operational, regulatory, and scientific discipline needed for broad clinical impact. If the sector can keep improving delivery, demonstrating safety, and proving scalable manufacturing, the next few years may turn in vivo editing from a breakthrough story into routine medicine.

Listen to all three episodes in this special in vivo series here or wherever you podcast.