CSO, Genomic Medicine
Cytiva
As the CSO for genomic medicine at Cytiva, I have numerous interactions with our customers, and I attend many scientific and industry events. It’s great to be able to get first-hand exposure to what is happening in our industry. As I look ahead to 2025, there are five big trends for genomic medicine.
Standardizing platforms and more knowledge sharing to accelerate the development of therapeutics for rare diseases
There is a lot of discussion in the biopharma industry about creating standard manufacturing platforms to enable the development of therapies to treat rare and ultra-rare diseases. By definition, relatively few patients live with these diseases compared to other diseases. Standardizing and industrializing a platform for gene therapies would enable regulatory bodies to accelerate the approval process because there would be standards and key parameters for pre-evaluation. We saw how collaboration between industry and regulatory bodies helped to safely accelerate the approval of mRNA vaccines and helped end the COVID-19 pandemic.
The FDA’s platform technology designation program (currently outlined in a draft guidance document) has been designed to help achieve the following goals:
• Streamline the development and approval process for therapies utilizing well-characterized platform technologies.1
• Reduce both the time and costs associated with bringing innovative therapies to market by leveraging existing data and methodologies.
• Decrease the risks associated with process scaleup, scaleout, and technology transfers.
If these goals are achieved it may also accelerate the availability of advanced treatments for patients with unmet medical needs, driving rapid progress in the field of genomic medicines. What a great potential outcome for patients!
Even for technologies not eligible for platform technology designation, developers must continue to leverage and share prior knowledge to speed up manufacturing and formulation development, and to demonstrate the robustness of unit operations.
2025 will be another big year for gene therapy
The science has proven that gene therapies are effective treatments, and they have given hope to patients and their families living with debilitating diseases. As of today, there are 2,041 potential gene-based therapies in various stages of clinical development.2
To increase access to gene therapies, we must continue to improve their safety, efficacy, and cost-effectiveness. Achieving these goals requires a laser focus on optimizing delivery systems, payload targets, and manufacturability. While viruses are proven and can be an effective delivery system for specific gene therapy needs, they are complex and costly to manufacture.
The emergence of new cell-line systems for AAV manufacturing such as packaging and producer lines brings the potential for increased process robustness and cost reduction. Because stable cell lines do not need the transfection step, this reduces the costs associated with that part of the development process. Stable cell lines also create greater consistency by decreasing the batch-to-batch variability. As is the case with mAbs, these cell lines can be further engineered to improve packaging efficiency, productivity, and—potentially—potency.
The clinical application of lipid nanoparticles (LNPs) is poised to expand due to their potential for precise targeting, as well as their manufacturability and scalability. When combined with gene editing tools, LNPs offer the potential to broaden their application in both in vivo and ex vivo settings.3 Process intensification is also a lever that needs to be pulled for all these modalities, in order to make the processes leaner and more efficient. We must continue investing and researching ways to reduce the costs associated with the manufacture of gene therapies.
Expanding application for CAR T-cell therapies
CAR T-cell therapies have proven to be effective treatments, and I believe there will be greater use of these therapies for hematopoietic tumors in 2025. There are many clinical trials underway globally to learn if they can be effective for solid tumors and autoimmune diseases. It is now possible to imagine a world where a patient could treat their autoimmune disease using their own cells, or even cells from healthy donors. That would truly be a game-changer for patients.
Overcoming the barriers of hard-to-treat diseases, such as solid tumors, demands further optimization of CAR T-cell therapies. Current efforts are increasingly focused on engineering T cells to improve their safety and efficacy. By utilizing efficient gene editing tools like CRISPR-Cas9, T cells can be engineered to exhibit significant enhancements in various aspects, including potency, toxicity, and immune compatibility. In this context, effective delivery systems are of paramount importance. LNPs have demonstrated superior performance in terms of cell viability and gene dosing tunability compared to electroporation.4 The synergy between LNP-based gene editing technologies and cell therapies is a trend that warrants close attention in 2025 and beyond.
Research to find the next RNA breakthrough will not slow down
Clinical research for RNA vaccines for infectious diseases and oncologic applications will continue at a rapid pace in 2025. In labs around the world, researchers are working to develop personalized cancer vaccines based on mRNA sequences of neoantigens from a specific patient they hope can be used as an adjuvant therapy. It’s exciting to think that this is even a possibility for cancer treatment.
While researchers are working to develop these mRNA vaccines, we must continue working closely with them to develop the tools, technologies, and services that will be needed to commercially manufacture these therapeutics.
Learning from the past experience of autologous CAR-T science advancing faster than its related manufacturing and solutions, we must continue working to advance the manufacturing technologies and solutions in preparation for potential breakthroughs in the RNA space.
Artificial intelligence has a role to play in the advancement of genomic medicines
From the Human Genome Project to the ENCODE project, the BRAIN Initiative, and the Human Cell Atlas (HCA), the last 30 years of research have generated huge data sets that are the foundation for genomic medicines. Artificial intelligence (AI) has already played a pivotal role in synthesizing and analyzing these data sets and has helped transform our understanding of the broad biological world. AI and machine learning have enabled clinicians to rapidly identify genetic variation and correlate mutations with genetic diseases. It is truly astounding how far we have come over several decades.
We are now using AI and machine learning tools to advance drug discovery, process development, and GMP manufacturing processes, and it will continue to play a critical role in these efforts. For example, these technologies are being used to formulate potential new therapeutics and predict off-target interactions that could impact safety and efficacy. For RNA-based medicines, AI tools can help predict and engineer the mRNA secondary structure to optimize protein expression, increase half-life, and eliminate potentially immunogenic structures from the medicine. In manufacturing, AI has the potential to improve efficiency, optimize processes, speed up batch release, and reduce costs.
AI is quickly becoming an important tool in the advancement of personalized and genomic medicines, particularly nucleic acid-based therapeutics. Scientists and researchers have more potential therapeutics for clinical pipelines than at any other time in history.
While AI and machine learning have played a part in getting us to where we are today, their impact is not yet realized in the clinical validation phase of drug development. We must continue working in earnest in 2025 to develop the tools that will enable researchers to safely accelerate the clinical validation phase and the manufacturing processes in order for genomic medicines to reach their full potential.
Daria Donati, PhD, is the CSO for genomic medicine at Cytiva.
References
1. FDA. Platform Technology Designation Program for Drug Development Guidance for Industry. Draft Guidance.
2. ASGCT Quarterly Report. Gene, Cell & RNA Therapy Landscape Report.
3. Kitte R, Rabel M, Geczy R, Park S, Fricke S, Koehl U, Tretbar US. Lipid nanoparticles outperform electroporation in mRNA-based CAR T cell engineering. Mol Ther Methods Clin Dev. 2023 Oct 18;31:101139. doi: 10.1016/j.omtm.2023.101139. PMID: 38027056; PMCID: PMC10663670.
4. Vavassori V, Ferrari S, Beretta S, Asperti C, Albano L, Annoni A, Gaddoni C, Varesi A, Soldi M, Cuomo A, Bonaldi T, Radrizzani M, Merelli I, Naldini L. Lipid nanoparticles allow efficient and harmless ex vivo gene editing of human hematopoietic cells. Blood. 2023 Aug 31;142(9):812-826. doi: 10.1182/blood.2022019333. PMID: 37294917; PMCID: PMC10644071.
