High-Capacity Adenovirus Vectors for Gene Therapy

Kilian Guse, PhD

Derek Jackson, BS, MA

Pacira Biosciences is currently developing enekinragene inzadenovec (PCRX-201), a clinical-stage gene therapy product based on the company's high-capacity adenovirus (HCAd) vector platform that is intended to treat osteoarthritis (OA) of the knee. At the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, held May 13 to 17, 2025, in New Orleans, LA, the company held a symposium focused on the HCAd platform and its potential utility in treating common diseases. The speakers at the symposium, which was entitled “High-capacity adenoviral vectors: advancing gene therapy beyond AAV to deliver cost-effective therapies for common diseases", included Brendan Lee, a professor of molecular and human genetics at Baylor College of Medicine; Derek Jackson, BS, MA, the vice president of cell & gene therapy product development at Pacira; and Kilian Guse, PhD, the vice president of genetic medicine platforms at Pacira.

The day before the symposium, CGTLive® spoke Jackson and Guse at the conference to learn more about the topics that would be covered. Guse and Jackson explained the expected role of the HCAd platform in the gene therapy ecosystem, emphasizing its potential for lowering necessary dose levels and reducing costs compared to adeno-associated virus (AAV) vector gene therapy.

CGTLive: Can you discuss Pacira's symposium at ASGCT?

Kilian Guse, PhD: Tomorrow, we'll have our symposium on HCAd vectors. In fact, PCRX-201, our OA lead candidate, is based on the HCAd platform. That's our first gene therapy coming out of this platform. We're looking to develop more gene therapies based on that platform in the musculoskeletal space, but also potentially in other areas.

Tomorrow, we'll have a symposium where Derek is going to highlight the PCRX-201 clinical data, I will highlight other potential applications for HCAd vectors, and then we'll have Professor Brendan Lee also speak about a little bit about the history of the HCAd platform. He's working at Baylor College of Medicine, where really the beginning of this platform took place, and he worked for decades on the platform, so he's actually the perfect person to talk about the history of that.

What do you expect some of the key takeaways of the symposium to be?

Kilian Guse, PhD: I think really the main takeaway should be that that the HCAd vector platform is suitable for developing gene therapies for prevalent nongenetic disease. The way I see it is that there are a lot of gene therapies that have been or are being developed for monogenetic rare disease, and a number of them are approved, and there's a lot of gene therapies in the pipeline with great clinical results. So I would say that gene therapy for monogenetic disease is validated now, and now I think we need to take gene therapy to the next level, which is developing them for prevalent nongenetic diseases. That's where the HCAd platform seems to be particularly suitable.

Derek Jackson, BS, MA: I would add to that, one of the things we like about adenovirus is its excellent transduction efficiency, which allows for lower doses. When you're in the common disease space, lower doses and cost is really an important parameter to a successful product. This has been an issue that the gene therapy field has been labeled with—it's "high cost therapy"—but we're taking the application in the PCRX-201 program, for example—it's a locally-administered to the knee product, doses are relatively low, and we think that we can price the product in a region that is appropriate for osteoarthritis, where there are already several therapies available to patients. We're using the HCAd platform to extend gene therapy into a competitive space for common disease, as Killian mentioned.

Is there anything else you want to add?

Derek Jackson, BS, MA: I'd like to share that recently Killian and his team joined Pacira and Killian, humbly, is the inventor of PCRX-201. At Pacira, we've been developing this candidate for quite some time now, and as we've continued the clinical validation of PCRX-201 specifically and the HCAd platform more broadly, it just made sense that we should start working together and harness the full power of this platform. We're really excited to to have this symposium and to let the world know that this is what we're about,

Kilian Guse, PhD: If I may add, we're very happy that we are now part of the Pacira group and that we can really take this HCAd platform to the next level. Before we had been an independent company, privately funded, and that can be challenging. Now within the Pacira group, I think we have much better resources and much better opportunities to really take the platform to the next level.

Derek Jackson, BS, MA: Together, we're going to bring gene therapy to the masses.

This transcript has been edited for clarity.

Click here to view more coverage of the 2025 ASGCT Annual Meeting.

REFERENCE
1. Pacira Biosciences to present new data on clinical immunogenicity of intra-articular PCRX-201 and its implications for dosing strategy in knee osteoarthritis. News release. Pacira BioSciences, Inc. May 2, 2025. Accessed July 8, 2025. https://investor.pacira.com/news-releases/news-release-details/pacira-biosciences-present-new-data-clinical-immunogenicity