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Demand for nucleic acid therapeutics (NATs) is increasing as mRNA-based products, oligonucleotide therapeutics and gene editing applications expand from niche rare diseases into mainstream, high-prevalence indications. An example of this is Zilebesiran, a novel RNA interference (RNAi) therapeutic that is currently advancing through late-stage clinical trials for the treatment of hypertension ^[1]. This illustrates a major sector shift, with hypertension being the leading cardiovascular risk factor worldwide, and is only one example of how NATs are expected to drive oligonucleotide drug substance demand to unprecedented multi-ton scales.

This rapid shift toward large patient populations is reflected in the global NAT CDMO market, which was valued at USD 20.3 billion in 2023 and is projected to reach USD 33.86 billion by 2030 ^[2]. As developers scale to meet rising demand, there is a growing pressure on manufacturing infrastructure that exposes risks. Relying on a fragmented supply chain distributed across multiple vendors jeopardizes clinical progression and complicates the path to a reliable commercial supply. A vertically integrated supply model resolves these vulnerabilities, stabilizing scale-up and ensuring consistent quality without the coordination delays of multi-vendor handoffs.

 

The Fragmentation Problem

In conventional NAT manufacturing, production is typically distributed across multiple vendors that are each responsible for individual processes such as supplying raw materials, oligonucleotide drug substance (DS) and drug product (DP) manufacturing, fill-finish and analytical testing. Although vendors are specialized in their operations, there is an increased risk of delays and misalignment with every handoff.

Root cause analysis and corrective action can slow when data, batch records and decision-making sit across different systems. Additionally, smaller developers may be deprioritized as vendor capacity is allocated to larger accounts, causing delays.

 

How a Vertically Integrated Model Stabilizes NAT Manufacturing

A vertically integrated supply model consolidates the full production workflow, from the synthesis of raw materials through to cGMP production and fill-finish, within a single organization operating under a unified quality system.

By controlling the supply chain end-to-end, a contract development and manufacturing organization (CDMO) can operate without the coordination challenges of fragmented models. Quality control is also standardized across processes and documentation, including batch records, which can be passed directly between teams at each stage.

 

Adaptable, Continuous Production

Each of the NAT modalities has its own set of material inputs and process requirements that a vertically integrated supply model aligns to ensure consistent quality control and reduce delays.

The oligonucleotide supply chain begins with highly specialized materials, such as phosphoramidites, nucleoside-loaded solid supports and ligands. These materials require multiple synthetic steps to produce and are subject to strict regulatory expectations. Synthesizing oligonucleotide DS and DP from starting materials requires a set of tightly controlled chemical reactions to minimize impurities being produced.

Moreover, chemoenzymatic ligation technology may be used, requiring a source of ligase, as well as specialized process knowledge to meet technical and regulatory requirements. Vertical integration is designed to mitigate supply chain risk and streamline the development of oligonucleotide therapeutics through the in-house production of starting materials and ligase at a commercial scale.

The same model of end-to-end control also applies to Hongene’s mRNA and CRISPR therapies. For mRNA-based products, integrated control over modified NTPs, enzymes, cap analogs and plasmid-derived DNA templates can help align synthesis, purification, LNP formulation and fill-finish.

Gene editing therapeutics can also require coordination across chemically synthesized sgRNA, mRNA-encoded Cas enzymes and lipid nanoparticle components. When these elements are managed across separate vendors, handoffs increase the risk of delay and misalignment.

 

What to Look for in an End-to-End CDMO Partner

Drug developers searching for a suitable end-to-end CDMO partner should look for evidence that the partner can support continuity from early development through to cGMP production and fill-finish. Evaluating factors such as scalable infrastructure, cross-functional expertise, regulatory-ready quality systems and operational flexibility assists this choice:

1. Scale with Continuity

   A partner that can support early development but lacks scale-up infrastructure can create a technology transfer burden at a critical stage. Conversely, a partner that is focused entirely on large-scale commercial manufacturing may also lack the responsiveness and collaborative depth that early-stage development requires.

2. Cross-Functional Expertise

   Interdisciplinary teams of subject matter experts are able to communicate within one supply chain to manage clearer decision-making and problem-solving.

3. Regulatory Readiness

   The selected CDMO should provide cGMP-compliant facilities and a robust quality system capable of supporting regulatory submissions to global health agencies. Moreover, traceability allows the CDMO to track raw materials throughout their life cycle to the end product, assisted by the required documentation and batch records. This streamlines the auditing process and regulatory submissions.

4. Operational Flexibility

   Operational flexibility is required because NAT programs can change as clinical, analytical or regulatory requirements evolve. Responsive processes allow teams to resolve issues and make technical decisions without losing quality oversight. As requirements change, a suitable CDMO should be able to adapt timelines, documentation needs and process requirements while maintaining clear accountability.

 

Securing a Scalable Supply Chain with a Vertically Integrated Model

The global CDMO market for nucleic acid therapeutics continues to grow, driven by the expanding clinical pipeline and the emergence of new cardiometabolic targets, all of which will require large-volume and specialized manufacturing infrastructure ^[3][4]. For drug developers bringing these therapeutics to market, CDMO partner selection must consider scalable infrastructure, quality oversight and documentation systems that can support later-stage requirements.

To find out more about how Hongene’s vertically integrated supply model is designed to address supply chain complexity, read Hongene’s full white paper on the topic.

Vertically Integrated CDMO Capabilities at a Glance

 

References

1. Verma, S.; Pradhan, A.; Thandi, P. Zilebesiran: An RNA Interference Agent—Its Need and Potential to Transform Hypertension Treatment. Egypt. Heart J. 78.1 (2026): 12. https://doi.org/10.1186/s43044-026-00724-9.
2. Nucleic Acid Therapeutics CDMO Industry Outlook 2024–2030. GlobeNewswire. October 10, 2024. https://www.globenewswire.com/news-release/2024/10/10/2961563/28124/en/Nucleic-Acid-Therapeutics-CDMO-Industry-Outlook-2024-2030.html
3. Youssef, M., Hitti, C., et al. “Enabling mRNA Therapeutics: Current Landscape and Challenges in Manufacturing.” Biomolecules. 13.10 (2023): 1497.
4. Ingle, R. G., & Fang, W. J. “An Overview of the Stability and Delivery Challenges of Commercial Nucleic Acid Therapeutics.” Pharmaceutics. 15.4 (2023): 1158.