The U.S. Food and Drug Administration’s recent restrictions on viral vector gene therapies due to cancer risks have sent ripples across the biotech industry. For years, viral vectors have been a cornerstone of gene and cell therapy. Still, these regulatory actions signal a pivotal moment, ushering in a new era where safety, scalability, and accessibility take center stage.
At the forefront of this paradigm shift is NanoCell Therapeutics, a biotechnology company pioneering non-viral DNA delivery for in vivo CAR-T therapy. Their novel approach aims not only to reduce risks associated with traditional viral vectors but to expand access to life-saving therapies that remain out of reach for most patients today.
A Turning Point in Gene Therapy
The FDA’s recent restrictions on viral vector-based therapies are not an isolated event. They reflect growing unease around the safety of these delivery systems. Chief among the concerns is insertional mutagenesis, a phenomenon where viral vectors integrate genetic material into the genome in ways that can inadvertently activate cancer-causing genes. While viral vectors have propelled the field forward, their risks are becoming harder to overlook as gene therapies expand to broader patient populations.
This regulatory shift has opened the door to non-viral platforms, which offer a different risk profile. NanoCell Therapeutics is among the leaders advocating for this transition, not by rejecting integration entirely but by engineering it more safely.
“Non-viral delivery of integrative DNA using transposase technology does not eliminate the risk of integration-related mutagenesis,” says Dr. Maurits Geerlings, CEO and President of NanoCell Therapeutics. “However, in comparison to viral vectors, which have a propensity to integrate in active gene regions, the Sleeping Beauty transposase that NanoCell uses has a more random integration profile and is theoretically safer than viral vectors.”
Geerlings notes that viral vectors have long been at the forefront of gene and cell therapy, creating substantial clinical experience and knowledge of the risks associated with these approaches. Non-viral vectors are gaining momentum but still need to demonstrate their efficacy and safety in the gene and cell therapy space. Nevertheless, they potentially offer several attractive features—such as scalability, lower immunogenicity, reduced cost of goods (COGs), and the potential for redosing—that could position them as strong alternatives to viral vectors.
Regulatory Scrutiny Spurs Innovation
While the FDA’s increased scrutiny of viral-based delivery methods creates urgency for alternatives, the path forward for non-viral platforms may not be free of regulatory hurdles. Dr. Jacek Lubelski, CTO of NanoCell, offers a nuanced perspective:
“It is too early to tell, but it is likely that safety assessments, such as vector copy number and integration site analysis, as well as the long-term, 15-year monitoring of patients, will apply to non-viral DNA-based platforms, as much as these measures apply to viral vectors,” he says. “There are other safety aspects of viral versus non-viral vectors that may lead to favoring non-viral platforms, but it is difficult to generalize, as each approach has its own specific risk/benefit profile.”
Redefining Manufacturing and Accessibility
NanoCell’s non-viral approach is also disrupting the economics and logistics of gene therapy. Traditional CAR-T therapies require hospital-based procedures, such as apheresis and ex vivo cell manipulation, which dramatically increase costs and limit accessibility to only a small fraction of eligible patients.
NanoCell’s approach addresses these challenges through its manufacturing advantages.
“The manufacturing of our tLNP vector has scalability potential and can be made available as a ready-to-use, off-the-shelf product,” says Geerlings. “We envision COGS on a per-patient treatment basis to be more favorable than ex vivo manufactured CAR-T therapies. Besides manufacturing costs, we envision significant cost savings by not requiring hospital-based treatment costs, such as apheresis and lymphodepletion.”
These advantages could be transformative for patients globally. “These cost reductions and the elimination of logistical hurdles, both for manufacturing and for the patient, would enable patient access to CAR and TCR therapies, including in countries where these treatments are not currently available,” adds Geerlings.
A Breakthrough in In Vivo Integration
One of the most scientifically impressive aspects of NanoCell’s approach is achieving stable DNA integration in T cells in vivo without viral vectors—a significant technical challenge in the field.
“Non-viral delivery of DNA into the nucleus of primary T cells is highly challenging and is influenced by multiple factors,” says Geerlings. “At NanoCell, we have dedicated several years to addressing this challenge by developing and optimizing multiple parameters in parallel.”
Changing the Patient Experience
Beyond safety and scalability, NanoCell’s vision includes improving the emotional and logistical burden on patients and their families.
“Conventional CAR-T therapy requires a tremendous amount of logistical organization for patients and their families,” says Lubelski. “Furthermore, the ‘vein-to-vein’ time between initial apheresis and ultimate treatment takes several weeks, which is precious time during which the patient’s condition can worsen.”
By shifting to in vivo delivery, patients may potentially be treated more quickly and in simplified settings, reducing both stress and disease progression during waiting periods.
An Industry on the Cusp of Transformation
While viral vectors still dominate the CAR-T landscape, NanoCell’s leadership believes the tide is turning.
“We generally see fields becoming crowded quickly in biotech where risk is perceived as being reduced due to precedent experience,” Lubelski notes. “To that end, we see in vivo CAR-T therapy being pursued by multiple companies either using viral vectors or RNA delivered through lipid nanoparticles. There is a desire for non-viral DNA-based delivery, yet development of this approach is lagging behind viral delivery. With increasing experience and awareness among investors, industry, and academia, we anticipate non-viral delivery will catch up and possibly become the preferred modality.”
If NanoCell’s predictions hold true, the future of gene therapy may look radically different in just a few years.
Redefining Success
For NanoCell, success isn’t defined by headlines or high valuations. It’s about impact.
“NanoCell’s success is defined by the benefit it can provide to the many CAR-T-eligible patients who are left out because of barriers to accessing existing CAR-T therapies,” Geerlings says. “We would celebrate the day when our tLNP-based therapies are available affordably to the wider patient population in countries that are typically left out of modern breakthrough therapies. This is the true definition of ‘success.’”
As the FDA and the industry rethink the risks and rewards of gene therapy platforms, companies like NanoCell Therapeutics are not just preparing for the next chapter—they’re writing it.
For more information, visit nanocelltx.com.
Daniel Casciato is a seasoned healthcare writer, publisher, and product reviewer with two decades of experience. He founded Healthcare Business Today to deliver timely insights on healthcare trends, technology, and innovation. His bylines have appeared in outlets such as Cleveland Clinic’s Health Essentials, MedEsthetics Magazine, EMS World, Pittsburgh Business Times, Post-Gazette, Providence Journal, Western PA Healthcare News, and he has written for clients like the American Heart Association, Google Earth, and Southwest Airlines. Through Healthcare Business Today, Daniel continues to inform and inspire professionals across the healthcare landscape.
