In a groundbreaking advance poised to disrupt the landscape of precision medicine, a European research collaboration has developed an innovative gene therapy delivery system that empowers hospital pharmacies to manufacture personalized nanomedicines on demand. This revolutionary device, known as NANOSPRESSO, merges cutting-edge nucleic acid therapeutics with lipid nanoparticle technology into a compact, portable manufacturing unit designed for in-hospital use. This approach could dramatically alter treatment paradigms for rare genetic disorders and expand equitable access to custom gene and RNA therapies worldwide, including in resource-limited settings.
Rare diseases, defined by the European Medicines Agency as those affecting fewer than five in 10,000 individuals, cumulatively impact approximately 300 million people globally, with around 36 million patients in the European Union alone. Despite their widespread collective prevalence, the traditional pharmaceutical development pipeline, with its reliance on centralized production of mass-market drugs, fails to adequately serve this diverse and fragmented patient population. The immense costs and complex logistics of producing individualized gene therapies have historically restricted access, leaving a significant treatment gap. NANOSPRESSO seeks to overturn these limitations by decentralizing the production of nucleic acid nanomedicines, tailoring therapies to patients’ unique genetic aberrations within hospital settings.
At the core of NANOSPRESSO lies the fusion of two validated biomedical technologies: nucleic acid therapeutics, which leverage RNA or DNA molecules to selectively target malfunctioning genes, and lipid nanoparticles (LNPs), engineered nanocarriers optimized for delivering these fragile molecules safely into cells. By encapsulating the nucleic acids within lipid carriers, the device ensures protection from enzymatic degradation and facilitates precise biodistribution, enabling the therapeutic cargo to reach the intended cellular targets effectively. The system’s microfluidic design mimics the precision and convenience of espresso machines, employing cartridge-based inputs that hospital pharmacists can load with lipid formulations and patient-specific genetic sequences to fabricate sterile, injectable nanomedicines on site.
This paradigm-shifting technology holds particular promise for the treatment of rare genetic diseases, many of which manifest early in life and often lack approved therapies due to the prohibitive costs associated with individualized drug development. Unlike conventional manufacturing, which caters to high-volume production and fails to economically justify small-batch therapeutics, NANOSPRESSO’s compact footprint and streamlined process could enable tailored medicines to be produced at the point of care. Such democratization of gene therapy manufacturing might significantly alleviate the disparities in healthcare access, bridging the gap between advanced medical technologies and under-resourced clinics across the globe.
The biological underpinnings of nucleic acid therapies are pivotal to their versatility. These therapeutics work by modulating gene expression through specifically designed RNA or DNA sequences that can silence, correct, or replace faulty genetic instructions responsible for disease phenotypes. Moreover, by altering the nucleic acid sequence payload, this treatment modality can rapidly pivot to address a myriad of conditions, ranging from monogenic inherited disorders, various malignancies, to infectious diseases where crucial viral or bacterial proteins need to be hindered. The high specificity of these therapies reduces off-target effects and enhances patient safety profiles.
NANOSPRESSO’s development has been spearheaded by a multidisciplinary team led by Professor Raymond Schiffelers at University Medical Center Utrecht. Their work builds on the successes of nucleic acid-based medicines, such as the mRNA vaccines deployed during the COVID-19 pandemic, demonstrating that clinically relevant, gene-targeted therapeutics can be produced efficiently and at scale. What sets NANOSPRESSO apart is its ability to condense the traditionally complex and resource-intensive manufacturing process into a user-friendly device operable by hospital pharmacists without requiring extensive specialized infrastructure.
Functionally, the device utilizes pre-loaded cartridges containing bespoke formulations of lipids and nucleic acids specific to the patient’s disease-causing mutation. These components are precisely combined within a sterile, closed-system microfluidic platform that facilitates controlled mixing and nanoparticle assembly in real time. The result is a homogenized suspension of nucleic acid-carrying lipid nanoparticles, formulated with rigor to meet stringent safety, efficacy, and sterility standards. The entire procedure circumvents the logistical and regulatory delays associated with centralized drug manufacturing and distribution, offering a just-in-time pharmaceutical manufacturing model.
Nevertheless, the introduction of such disruptive technology poses significant challenges to existing healthcare and regulatory frameworks. The notion of hospital-based production of gene therapies requires a re-evaluation of quality control systems, approval pathways, and liability construct to ensure patient safety without stifling innovation. The NANOSPRESSO team has proactively initiated dialogues with regulators and industry stakeholders to delineate pathways for compliance and integration, drawing parallels to the historical practice of pharmaceutical compounding, where pharmacists formulated personalized medicines prior to the industrialization of drug production.
Ethical and economic considerations also emerge as critical discourse points. By empowering local manufacturing, NANOSPRESSO could reduce drug costs substantially, making precision nanomedicine accessible beyond affluent nations and tertiary care centers. This localization may reduce healthcare disparities, particularly in rural or low-income regions traditionally marginalized in advanced therapy availability. However, implementing such technology demands robust training programs, standardized operating protocols, and integration within hospital pharmacy workflows to safeguard against variability and ensure reproducible therapeutic quality.
Currently, NANOSPRESSO prototypes are in active development, with ongoing research addressing technological refinement, pharmacological efficacy, biosafety, and integration logistics. Investigations are underway to validate the device’s performance across a spectrum of nucleic acid sequences and lipid formulations, simulate clinical deployment scenarios, and engage with healthcare providers to tailor operational models. The overarching ambition is to establish a scalable platform that seamlessly embeds into healthcare environments, enabling clinicians to harness personalized nanomedicines for diverse rare diseases and beyond.
By seamlessly bridging the gap between cutting-edge biotechnology and practical clinical application, NANOSPRESSO represents a beacon of innovation in the realm of personalized medicine. Its potential to transform the treatment landscape for millions suffering from rare genetic diseases is unparalleled, offering a vision of healthcare where medicines are no longer mass-produced commodities but precise, patient-customized interventions fabricated at bedside. As this technology matures and regulatory frameworks evolve, the promise of democratized gene therapy production draws nearer, heralding a new era of accessible precision health.
The project NANOSPRESSO-NL, supported by the Netherlands Science Agenda and the Netherlands Organization for Scientific Research, exemplifies how collaborative, interdisciplinary efforts can enable paradigm shifts in medical technology. The convergence of molecular biology, bioengineering, and clinical pharmacy embodied in NANOSPRESSO paves the way for a future where innovation transcends traditional manufacturing bottlenecks and empowers local healthcare providers to deliver next-generation therapies to patients irrespective of geography or resource constraints.
Subject of Research: Not applicable
Article Title: NANOSPRESSO: toward personalized, locally produced nucleic acid nanomedicines
News Publication Date: 26-Jun-2025
Web References: 10.3389/fsci.2025.1458636
Keywords: Personalized medicine, gene therapy, nucleic acid therapeutics, lipid nanoparticles, rare diseases, drug delivery systems, precision medicine, microfluidics, nanomedicine, healthcare equity, gene delivery, pharmacogenetics
