Rethinking Academic Translation In CGT: Inside The RISE Framework At Mass General Brigham

By Erin Harris, Editor-In-Chief, Cell & Gene
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As the CGT space continues its rapid growth, with more than 30 FDA-approved therapies and a surge in clinical trials and early-stage research, academic medical centers (AMCs) remain pivotal in driving scientific progress. Yet, moving these innovations from the lab to the clinic remains a complex and costly endeavor. In response, at the ASGCT 28^th Annual Meeting in New Orleans, Nandhitha Uma Naresh, Ph.D., of the Mass General Brigham Gene and Cell Therapy Institute, presented the RISE framework — a strategic approach aimed at strengthening AMC capabilities in advancing CGT programs. Centered on Resource sharing, Interdisciplinary collaboration, Sustainable funding, and Educational outreach, RISE offers a structured path to help bridge translational barriers and ensure that promising academic discoveries are not lost in the difficult transition from bench to bedside. I caught up with Dr. Naresh and one of the study authors on the RISE Framework, Nathan Yozwiak, Ph.D., Head of Research, Mass General Brigham Gene and Cell Therapy Institute, to learn more about RISE and its impact on the CGT space. Here’s our discussion.

Explain the origin of RISE: what key challenges in the academic CGT ecosystem prompted the creation of this framework, and how did you arrive at Resource Sharing, Interdisciplinary Collaboration, Sustainable Funding, and Educational Outreach as the four pillars?

The RISE framework originated in response to the persistent challenges seen in the academic translational research, where many promising GCT programs at the late-pre-clinical stage fail to advance towards the clinic due to insufficient resources and systemic gaps in support. These programs often require resource-intensive studies using large animal models, manufacturing scale-up, combined with a high-degree of cross-functional expertise. However, the late pre-clinical stage is unfortunately where academic innovation stalls, entering what is referred to as the “translational valley of death.”

At the Mass General Brigham Gene and Cell Therapy Institute, we recognized the need to support the programs at this stage and overcome barriers through building a comprehensive infrastructure. This led us to create the RISE strategy, where each pillar is directly informed by the operational and structural needs within our own GCT research and clinical community, and that ultimately seeks to improve patient access to GCTs by reducing the development costs. The RISE framework contains the following four pillars:

1. Resource Sharing addresses challenges related to limited access many investigators face in obtaining high-quality, cost-effective GCT components, such as circular RNA and viral vectors. By leveraging centralized research core facilities, we have been able to provide these critical materials at scale and at a lower cost, ensuring that academic programs are not hindered by manufacturing barriers.
2. Interdisciplinary Collaboration reflects a unique strength of our institution, which brings together clinicians, scientists, and patients across a vast healthcare and research network. We designed RISE to systematically integrate insights from a wide array of stakeholders, recognizing that successful GCT development relies on alignment from discovery through clinical application.
3. Sustainable Funding is essential to help academic programs reach key inflection points along the translational path. Through internal funding mechanisms, we help advance these programs, positioning them for follow-on investments and long-term development.
4. Educational Outreach is grounded in our teaching role within academia as well as our belief that sustaining a robust GCT development pipeline both now and, in the future, requires continuous investment in people, which includes fostering a community of well-informed scientists and healthcare professionals.

AMCs often incubate groundbreaking science, but translating those discoveries into therapies remains a hurdle. What structural or cultural shifts do AMCs need to make to better support this kind of translational work under the RISE model?

In addition to adopting and implementing the RISE framework, we urge the GCT community in AMCs to consider several actionable structural and cultural shifts to increase translational impact while incubating next-generation scientific breakthroughs.

Structural shifts:

• Centralizing institutional facilities that manage shared GCT resources and expertise across various departments
• Creating novel funding mechanisms that empower academic investigators to pursue innovative entrepreneurial ideas unconstrained by traditional grant pathways
• Building in-house business development capacity that reduces reliance on external partners for strategic alignment from discovery through in-human trials
• Creating forums and discussion platforms for exchanging ideas that can ultimately help accelerate inter- and intra-institutional growth

Cultural shifts:

• Cultivating a collaborative mindset among academics, scientists, clinicians, patient advocates and regulators who drive translational advancement through shared goals
• Promoting a culture of risk tolerance that drives scientific potential and patient-centric impact over purely commercial viability
• Fostering near-term academic progress and institutional learning, while building a foundation for long-term returns
• Building resilience and strategic flexibility to weather the challenges of volatile and uncertain funding climates

In terms of Resource Sharing, how can institutions practically break down silos and share core infrastructure, talent, or regulatory expertise to accelerate CGT development?

Large AMCs such as Mass General Brigham house a rich, multifaceted ecosystem of research and medical subspecialties, including numerous clinical development programs across departments. However, many of these efforts may be siloed within individual research groups. Centralized institutes with dedicated efforts for GCT development such as the MGB Gene and Cell Therapy Institute (GCTI) play a crucial role in breaking down these silos by acting as integrative hubs. At GCTI, we foster collaboration across disciplines by serving as a central connector (the “hub”) that links research efforts across departments (“spokes”), enabling partnerships that might not otherwise emerge organically. This includes proactively identifying scientific and clinical programs with complementary strengths and facilitating structured cross-talks for joint innovation.

Beyond serving as a liaison between groups, centralized organization can invest in shared services that support multiple research teams with similar needs, reducing redundancy and avoiding duplication of efforts across individual labs. For instance, GCTI launched a dedicated RNA Therapeutics Research Core in 2023 to provide circular RNA manufacturing services. Prior to this, few investigators within MGB and other academic institutions had access to this cutting-edge modality. Since its launch, the number of research groups utilizing circular RNA technology has nearly tripled, accelerating the pace of discovery in this next-generation space.

Additionally, institutions can promote knowledge sharing by disseminating regulatory insights across programs. For example, when a centralized institute like GCTI facilitates early FDA interactions such as INTERACT or pre-IND meetings for a rare disease gene editing program, the regulatory learnings from that experience can be shared with other teams working on similar modalities, even in different clinical specialties. This approach helps accelerate development across the AMC.

The Sustainable Funding piece is particularly difficult in early-stage translational science. What innovative funding mechanisms or partnerships do you believe AMCs should pursue to keep promising CGT programs alive past proof-of-concept?

MGB GCTI’s Spark program enables sustainable funding for advanced cell and gene therapy research by incubating preclinical programs in-house and securing subsequent non-dilutive and hybrid funding. We invested over $2 M to date across multiple research programs that are in the late pre-clinical stage. The Spark program is designed to advance therapies beyond proof-of-concept by supporting pivotal discovery milestones such as pharmacology/toxicology studies in large animal models and regulatory milestones including pre-IND, IND submissions, and ultimately, first-in-human trials. By retaining programs within the academic setting through key inflection points, institutions like GCTI can generate novel IP and value while maintaining greater control over therapeutic direction. A portion of the value created from such programs can then be realized by re-investing into the portfolio for expansion and further development.

To support extended incubation, institutions like GCTI need to actively seek funding from a variety of external sources that can enable de-risking the development path within the academic environment.

How does RISE encourage interdisciplinary collaboration, especially between clinicians, basic scientists, and manufacturing experts, to avoid bottlenecks during clinical translation?

The RISE framework recognizes that successful GCT translation requires interdisciplinary collaboration amongst a diverse group of experts and a culmination of their efforts. The Spark funding initiative supports a portfolio of assets each on a clinical trajectory that inherently requires coordinated contributions from basic scientists, clinicians, and manufacturing experts at every stage. For example, the early-stage bench discoveries for all assets are shaped through joint efforts between MGB research scientists and clinicians, who work together to optimize therapeutic targets into viable candidates that address critical unmet medical needs. As programs move toward translation, GCTI integrates in-house manufacturing expertise early in development. Early engagement allows teams to preemptively address challenges in process development, assess GMP feasibility, and align manufacturing strategies with clinical endpoints. Such foresight is critical in avoiding downstream bottlenecks that often delay translation. In addition, GCTI provides regulatory oversight and facilitates FDA interactions as the programs advance past pre-clinical discovery. Therefore, by centralizing regulatory, manufacturing, and funding capabilities, GCTI enables cross-functional teams to work in unison from discovery through first-in-human trials.

You’ve said that without focused institutional support, many CGT programs risk dying in the ‘valley of death.’ What does it take for a therapy to make it across that valley within an academic setting, and how can RISE help de-risk that path?

When an academic lab wants to translate their promising new gene therapy into the clinic, typically at a fairly early stage, they would license out the technology to a biotech or pharma for the remaining clinical development. But what if we wanted to incubate more of that development in an academic hospital across a range of new technologies, leveraging our scale of subject matter experts and patient communities? That is where infrastructural scale is needed. A GCT-themed institute that can assist investigators in this clinical journey within the AMCs, helping programs with required animal safety studies, manufacturing process development, and regulatory processes. It is unreasonable to expect each individual lab to recreate or contract out everything needed for vertical scale-out to make a drug. This is where GCTI comes in. We can provide shared expertise and materials that can be leveraged across multiple GCT programs. And if we build in the right resources, we can advance multiple clinical programs simultaneously, de-risk this path, reach human trials more efficiently, and traverse the translational canyon before partnering with industry to bring it to market with commercial scaling. This is how we hope to leverage our core competencies and help advance new therapies into investigator-led first-in-human trials.