Opening the Door: The Technology Scaling the Next Era of Emerging Therapies
As emerging therapies target increasingly niche genetic pathways, the adoption of AI modeling, organoids, and advanced AAV delivery is becoming essential to ensure successful clinical progression and patient access.
Thanks to the foundational work of the Human Genome Project, which was completed over two decades ago in 2003 (1), biopharmaceutical research and development has made great strides forward. With this improved understanding of the human genome, it has been possible for researchers to gain better genetic insights into different diseases, allowing for novel, emerging therapies to be developed that are not only targeted and more effective for patients but also have fewer adverse side effects (2,3).
Translational Bridges
As drug developers target increasingly specific pathways and pursue novel and ever more complex molecules, it has been necessary to tackle R&D more efficiently to ensure successful clinical progression is possible. To help improve efficiencies in drug discovery, early development, and beyond, industry has started to adopt various technology-driven approaches.
A prime example of technology providing transformative results early on in the drug discovery and development stages can be seen in the application of artificial intelligence (AI) and machine learning (ML). By using these tools, researchers can perform various tasks, such as creating disease models, simulating molecular interactions, and predicting clinical outcomes, precisely and rapidly (4–7). Ultimately, the speed and precision afforded by AI and ML is helping to overcome the limitations of traditional approaches, which were more of a trial-and-error format and resulted in high attrition rates (8).
Organoids — three-dimensional tissue cultures derived from stem cells with the ability to self-organize and self-renew — are also helping to bridge the translational gap between research and the clinic, particularly for emerging and personalized medicines. These 3D models provide researchers with a human-first platform that can be used for high-throughput screening and disease modeling (9,10).
The benefits of organoid technology are particularly profound within the fields of personalized oncology and rare genetic disorders where developers can create patient-specific organoids. These individualized models can then be used to test therapeutic candidates against a patient’s unique genetic background prior to administration. By taking this approach, it is possible to significantly de-risk the development process and improve the predictive accuracy of toxicology studies (11–13).
However, the technology is not without its limitations. It has been reported that current organoids often have inadequate vascularization, limited maturity, and variable complexity. Additionally, there are insufficient tools available to monitor the structural-functional activity of the organoids (14).
To overcome the limitations of organoid culture, organoids-on-a-chip technology has been developed. This technology combines organoids with microfluidic chip technology to allow for dynamic and precise control over the organoid microenvironment (15).
Regulatory Consensus on Organoids
The regulatory landscape regarding organoid-derived data is undergoing a paradigm shift, catalyzed by the landmark FDA Modernization Act 2.0, which officially removed the requirement for animal testing in the development of new drugs if alternative methods can provide sufficient safety and efficacy data (16). As a result, there is an active push to incorporate organoid data into Investigational New Drug (IND) filings, particularly when animal models are deemed non-predictive or when the therapeutic target is uniquely human, as is the case with many gene therapies and antisense oligonucleotides.
Biotech company, Qureator, recently reached a milestone by achieving an FDA IND approval in oncology using human vascularized organoid efficacy data alone. The company generated preclinical data using its proprietary AI-powered vascularized tumor immune microenvironment (vTIME) organ-on-a-chip platform, which was then used by its partner, SillaJen, for the IND approval of a combination therapy (17).
“This milestone demonstrates how close collaboration between regulators and innovators can accelerate the transition to human-relevant testing,” remarked Dr. Kyu Baek, Qureator CEO, in a company press release about the achievement (17). “By replacing animal POC studies with more predictive, human-based efficacy models, we are reshaping how preclinical data translate into clinical outcomes.”
Delivering Complex Disease Therapies
Of course, the research into such promising, emerging therapies would be redundant if they have no way of being delivered to the patient. An added layer of complexity impacting delivery of emerging therapies can be the complexity of the diseases being treated. For example, to treat diseases such as muscular dystrophy and Parkinson’s disease, developers are investigating in vivo gene therapies, which, in order to be successfully delivered, need to overcome issues related to tissue tropism and cargo capacity.
“Adeno-associated viral vectors (AAV vectors) carry potential to address multifactorial and progressive diseases for multiple reasons,” confirms Carey Connelly, Senior Director of Process Development at Catalent. “First, engineered capsids exhibit improved tropism, better tissue penetration, and reduced off-target exposure. The resulting potency increase and potential for lower dosing provide an important advantage, especially for systemic and CNS [central nervous system] indications.”
These engineered AAV capsids have been designed to bypass the liver and cross physiological barriers, such as the blood-brain barrier, with higher efficiency. As the capsids are more precise, lower systemic doses are needed and the risk of triggering a patient’s immune response is lowered (18).
“Second,” continues Connelly, “payload modularity enables increasingly complex therapeutic mechanisms including combinatorial designs (e.g., gene + regulatory RNA), dual AAV approaches (split genes and intein-mediated reconstitution for larger proteins), and finely tuned gene regulation using tissue-specific, inducible, or synthetic control elements.”
“Third, the sustained expression from a single dose benefits chronic conditions that require continuous therapeutic activity,” Connelly asserts. “Finally, intensified upstream processes and improved plasmid systems are driving higher yields and more consistent production.”
References
National Human Genome Research Institute. The Human Genome Project. Genome.gov (accessed March 10, 2026).
Wellcome. Genomics: How Unlocking our Genes is Transforming Healthcare. Article, Jan. 29, 2025.
Wellcome. The Human Genome Project: A New Era of Scientific Progress. Article, Feb. 6, 2025.
Moingeon, P.; Kuenemann, M.; Guedj, M. Artificial Intelligence-Enhanced Drug Design and Development: Toward a Computational Precision Medicine. Drug Discov. Today2022, 27 (1), 215–222.
Bassey, G.E.; Daniel, E.A.; Okesina, K.B.; Odetayo, A.F. Transformative Role of Artificial Intelligence in Drug Discovery and Translational Medicine: Innovations, Challenges, and Future Prospects. Drug Des. Dev. Ther. 2025, 19, 7493–7502.
Oyejide, A.J.; Adekunle, Y.A.; Abodunrin, O.D.; Atoyebi, E.O. Artificial Intelligence, Computational Tools and Robotics for Drug Discovery, Development, and Delivery. Intell. Pharm.2025, 3 (3), 207–224.
DrugPatentWatch. How Machine Learning is Recoding the Future of Drug Discovery. Blog, Aug. 3, 2025.
Hinkson, I.V.; Madej, B.; Stahlberg, E.A. (on behalf of the ATOM Consortium). Accelerating Therapeutics for Opportunities in Medicine: A Paradigm Shift in Drug Discovery. Front. Pharmacol., 2020, 11, 770.
Weng, G.; Tao, J.; Liu, Y.; et al. Organoid: Bridging the Gap Between Basic Research and Clinical Practice. Cancer Lett.2023, 572, 216353.
Xu, M.; Kong, D.; Sun, S; et al. Organoids for Disease Modeling and treatment: State-of-the-Art.Exp. Hematol. Oncol. 2026, 15, 10
Li, R.; Wu, Y.; Zheng, Z.; et al. Organoids in Cancer Research and Regenerative Medicine: Current Status, Challenges, and Future Prospects. MedComm2026, 7 (1), e70575.
Song, S.; Liu, Z.; Wang, Y.; Gong, B. Human Organoids and Their Application in Tumor Models, Disease Modeling, and Tissue Engineering. Med. Bull.2025, 1 (1), 17–36.
DelveInsight. 6 Groundbreaking Applications of Organoids that are Changing Healthcare. Blog, Nov. 6, 2024.
Fan, X.; Hou, K.; Liu, G.; et al. Strategies to Overcome the Limitations of Current Organoid Technology — Engineered Organoids. J. Tissue Eng. 2025, 16. DOI: 10.1177/20417314251319475.
Papamichail, L.; Koch, L.S.; Veerman, D.; Broersen, K.; van der Meer, A.D. Organoids-on-a-Chip: Microfluidic Technology Enables Culture of Organoids with Enhanced Tissue Function and Potential for Disease Modeling. Front. Bioeng. Biotechnol.2025, 13, 1515340.
Zushin, P.-J.H.; Mukherjee, S.; Wu, J.C. FDA Modernization Act 2.0: Transitioning Beyond Animal Models with Human Cells, Organoids, and AI/ML-Based Approaches. J. Clin. Invest.2023, 133 (21), e175824.
Qureator. Qureator Achieves World’s First FDA IND Approval Using Only Human Vascularized Organoid Efficacy Data. Press Release, Oct. 27, 2025.
Xu, X. Strategies of AAV Capsid Engineering for Targeted Delivery to Brain, Muscle, and Retina. Front. Mol. Biosci. 2026, 12, 1750807.
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