The advanced therapeutic medicinal product (ATMP) sector is rapidly expanding, offering transformative treatments for a wide range of conditions. Revolutionary gene editing technologies are helping to drive this growth by enabling the treatment of diseases at the genetic level.
Despite its enormous potential, gene editing is a relatively new therapeutic space, and developers face a steep learning curve, unique manufacturing challenges and limited access to expensive production technologies. Partnering with an experienced contract development and manufacturing organization (CDMO) can help overcome these hurdles, offering an innovative approach to gene editing development and manufacturing. In particular, the rise of “all-in-one” gene editing CDMO solutions is helping transform the way gene editing therapies are developed and manufactured
In this article, Melanie Cerulllo, Chief Quality and Regulatory Officer at ReciBioPharm, explores how CDMOs with all-in-one gene editing solutions are helping to drive the progression of the gene editing space. She also examines the strategies developers can take to scale up production, meet gene editing demands and deliver revolutionary treatments to the patients who need them.
The Expanding ATMP Space and the Rise of Gene Editing
The growing number of promising ATMPs in development offer a groundbreaking new approach to treating various diseases, including cancers, cardiovascular diseases, immune disorders and neurological conditions.1 In particular, CRISPR-Cas9 and other gene editing technologies are driving a revolution in pharmaceutical development and manufacturing by providing the tools to precisely target and modify DNA sequences and treat a wide array of diseases at the genetic level.
The potential of gene editing technologies is reflected in the current market dynamics. There are now over 425 companies engaged in developing and applying CRISPR vectors, including technology vendors, established pharmaceutical companies and emerging start-ups.2 The global gene editing market, valued at $5.3 billion in 2023, is projected to be worth $10.6 billion by 2028, growing with a compound annual growth rate (CAGR) of 15%.3 The first CRISPR-based gene editing product, CASGEVY®, has also recently been approved, contributing to this market growth.4
As the gene editing market expands, companies are investing in the development of next-generation technologies. From the first pioneering gene editing approaches, such as insertion and deletion (indel) formation and gene knockdown/knockout using CRISPR, the field is progressing towards individual base editing using advanced editing tools and engineered proteins.
Together, this rapid expansion and innovation make gene editing an exciting sector with the potential to benefit patients on a global scale. However, the development and manufacturing of these revolutionary technologies are not without challenges.
Understanding Gene Editing Challenges
Developing and manufacturing gene editing therapies is a complex and multifaceted process requiring specialized expertise, sophisticated infrastructure, and stringent quality control. From the design and engineering of gene editing components to supply chain constraints and scaling-up processes, developers face hurdles across every stage of drug development and manufacturing.
Complex Component Engineering and Manufacturing Processes
Gene editing therapies rely on either viral plasmid vectors or non-viral vectors to deliver the DNA editing components into cells. Both delivery methods present unique manufacturing challenges.5 Viral vectors, such as adeno-associated viruses and lentiviruses, require specialized cell lines, comprehensive purification processes and stringent quality control measures to ensure the safety and efficacy of gene editing products. Viral vectors provide high transduction efficiency but can initiate an immune response and have cargo limitations, leading to the exploration of non-viral vectors, such as extracellular vesicles (EVs) and lipid nanoparticles (LNPs). Non-viral approaches can have lower efficiency compared with viral vectors but are generally considered safer and can be applied in a wider range of situations.5 Gene editing developers must assess the advantages and disadvantages of viral or non-viral delivery methods when developing products.
Single-guide RNA (sgRNA) is a critical component of gene editing technologies like CRISPR-Cas9, as it guides the editing machinery to target DNA sequences. However, it can be challenging to consistently produce high-quality sgRNA, which can impact the efficiency and specificity of gene editing products. In addition, once the components have been combined in the final formulation, the product must undergo sterile fill and finish, adding another layer of complexity.
Accessing Expertise and Experience
Developing gene editing products requires a diverse, multidisciplinary team of experts with backgrounds in molecular biology, cell culture, virology, regulatory affairs, and clinical development. For smaller and emerging companies with limited resources, assembling a team with the necessary experience can be difficult.
Scaling-Up Processes and Supply Chain Challenges
As gene editing therapies progress through development, manufacturing processes must be scaled to meet the changing product demands for clinical trial materials and commercial production. However, manufacturing gene editing therapies often requires specialized facilities and equipment, such as bioreactors capable of maintaining precise conditions, high-performance liquid chromatography (HPLC) systems for purifying gene editing components and multiple analytical capabilities, including mass spectrometry, for quality control. Access to this equipment can be a significant bottleneck, creating capacity constraints, especially as the field expands and more therapies enter clinical development.
Another consequence of the complexity of gene editing products is that their supply chain can be complicated, involving multiple suppliers of raw materials, reagents, and equipment. Ensuring a reliable and consistent supply chain is crucial for successful manufacturing but is a challenge and developers often have to partner with multiple suppliers and outsourcing companies to source all required components.
Overcoming Gene Editing Challenges with All-In-One CDMO Solutions
Developers must effectively navigate the challenges in gene editing development and manufacturing to unlock the full potential of their revolutionary products. One strategy for overcoming these hurdles is to partner with gene editing CDMOs with a strong track record in the ATMP space that offer a wide range of services to support gene editing therapy production. CDMOs with all-in-one services, including both viral and non-viral delivery capabilities, can help simplify production for developers, minimizing the need to coordinate with multiple partners and stakeholders to source all necessary components. In addition, relying on an all-in-one CDMO with core RNA competencies enables companies to take advantage of existing robust quality systems and processes while also benefiting from experience in manufacturing complex biomolecules.
These CDMOs may also leverage strategic partnerships with other CDMOs to provide gene editing developers with an even greater range of services that complement one another. For example, a CDMO specializing in mRNA bioprocessing and LNP vector production could partner with another CDMO with expertise in high-quality sgRNA production using ligation synthesis to deliver a complete solution for gene editing therapies from the same facility. As a result, the CDMO can ensure the highest quality sgRNA while supporting scalable manufacturing and accelerated clinical translation. These collaborations create a single point of contact for all development and manufacturing needs.
Leveraging all-in-one CDMO partnerships also enables gene editing developers to benefit from:
Streamlined and reduced risk
Integrating all aspects of the development process reduces complexity and leads to faster development timelines while minimising delays and setbacks through seamless coordination. Manufacturing time can be reduced by eliminating the shipping of components from different vendors and the transport of multiple product lots.
Enhanced quality and regulatory compliance
End-to-end control over the manufacturing process ensures the highest quality standards and product consistency, ensuring adherence to Good Manufacturing Practice (GMP) standards.
Cost-effectiveness
By outsourcing development and manufacturing activities, gene editing developers can avoid significant capital investment and free up resources for other priorities. Additionally, all-in-one solutions can be more cost-effective than engaging multiple vendors, helping to avoid costly delays and rework.
Access to expertise, experience, and infrastructure
CDMOs possess extensive knowledge and experience, gained from working on multiple clinical programs. This enables them to track which strategies are successful and how these broad learnings can be applied to each program. Combined with access to cutting-edge facilities and equipment, this expertise provides comprehensive support throughout development and manufacturing processes.
Scalability and capacity
CDMOs specializing in gene editing development and manufacturing have the capacity and defined processes to scale up to meet the varying production demands of clinical trials and commercialization. This capacity also enables CDMOs to offer flexible manufacturing solutions to accommodate changing needs.
Ultimately, the goal of gene editing companies is to accelerate the development of safe and effective therapies, bringing treatments to patients with previously untreatable diseases. All-in-one CDMO solutions represent a significant step towards this goal, offering a streamlined and integrated approach to reduce the complexities and costs associated with gene editing development. By consolidating expertise, infrastructure and resources, these solutions empower developers to focus on innovating and advancing the frontiers of gene editing technology. This collaborative model paves the way for a future where gene editing therapies are more affordable and readily available to those who need them most.
Preparing for the Future of Gene Editing
Gene editing therapies hold immense promise for treating a wide range of diseases and improving human health. As this field continues to evolve rapidly with new product approvals and the emergence of next-generation editing platforms, we are uncovering more opportunities to deliver life-changing treatments to patients.
The future of gene editing holds immense promise, but navigating the rapidly evolving landscape and complex manufacturing processes will require a new era of collaboration. By partnering with CDMOs who embrace cutting-edge technologies and prioritize strategic alliances, developers can unlock the full potential of gene editing. This collaborative approach will be crucial for overcoming challenges, accelerating development timelines, and ultimately delivering life-changing therapies to patients faster and more efficiently. The rise of comprehensive gene editing solutions offered by CDMOs signals a future where collaborative innovation paves the way for groundbreaking advancements in medicine.
References
- Hanna E, Rémuzat C, Auquier P, Toumi M. Advanced therapy medicinal products: current and future perspectives. J Mark Access Health Policy. 2016 Apr 25;4. doi: 10.3402/jmahp.v4.31036. PMID: 27123193; PMCID: PMC4846788.
- https://www.pharmaceutical-technology.com/data-insights/innovators-crispr-vectors-pharmaceutical/
- https://www.marketsandmarkets.com/Market-Reports/genome-editing-engineering-market-231037000.html
- https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease
- Taghdiri M & Mussolino M. Viral and Non-Viral Systems to Deliver Gene Therapeutics to Clinical Targets. Int J Mol Sci. 2024 Jul 4;25(13):7333. doi: 10.3390/ijms25137333. PMID: 39000440; PMCID: PMC11242246
Author Details
Melanie Cerullo, Chief Quality and Regulatory Officer, ReciBioPharm
Publication Details
This article appeared in Pharmaceutical Outsourcing:Vol. 26, No.1 Jan/Feb/Mar 2025Pages: 12-14