Over 30 pilot programs worldwide are now sequencing newborn genomes, collectively screening tens of thousands of infants. Yet no governance framework exists to protect the resulting data from breaches, commercial exploitation, or institutional misuse. I argue that whole genome sequencing at birth should be recognized as a universal right, what I term genomic sovereignty . Under this model, each newbornâs genome is sequenced shortly after birth and delivered to the parents on an encrypted physical device, a genomic birth certificate, with no institutional copy retained. The sequencing facility purges its records upon delivery, and zero-knowledge proof protocols ensure that no traceable metadata links the genome to the childâs identity. Parents serve as temporary custodians until the child reaches adulthood and assumes full control over the data, including the right to re-encrypt, seek clinical interpretation, participate in research, or decline engagement entirely. This approach eliminates the centralized databases that have proven vulnerable to breaches and commercial exploitation, as demonstrated by recent high-profile data breaches and corporate bankruptcies in the commercial genomics sector. The genomeâs lifelong value as a health resource, one that appreciates as medical knowledge advances, means that data acquired at birth will become increasingly informative over decades. Health systems already administering newborn screening are the natural stewards of this initiative, ensuring equitable access regardless of geography or income. As sequencing costs approach $100 per genome and converge with what public health systems already spend on traditional newborn screening, the economic and ethical case for universal implementation becomes compelling.
The NANOSPRESSO project, described by Senti et al. in their lead article (Senti et al. 2025), is being developed to address the immense unmet medical need in the rare disease and rare cancers communities that are currently underserved by pharmaceutical industry and healthcare providers. The current situation in rare diseases, with small patient numbers (sometimes with only a single case reported worldwide) and substantial drug development costs, makes it difficult for the pharmaceutical companies to recoup their investment in this field.These commercial disincentives, combined with an uncharted regulatory landscape, impede the translation to the clinic of the scientific advances in development of nucleic acid-based therapeutics (NBTs) achieved in recent years that could have already significantly improved the lives of many patients with rare diseases and some rare cancers (Cheerie et al. 2023, Qian et al. 2025, Khorkova et al. 2023).Although the exact proportion of genetic diseases treatable by formulated NBTs (fNBTs) potentially produced by NANOSPRESSO is hard to calculate, a rough estimate based on the known types of pathogenic mutations and the proportions of genes amenable to regulation by multiple endogenous mechanisms that can be engaged by NBTs shows that it could be significant. However, in spite of the plethora of known NBT-based approaches that can be used in the treatment of genetic diseases caused by point mutations or insertions/deletions, substantial current practical challenges in this field can limit their impact (see Supplementary Materials).Although the first successful example of an "n=1" NBT (i.e., one produced for a single individual) was published in 2019 (Kim et al. 2019) it has not been widely replicated, with only 26 other cases over 16 years (Cheerie et al. 2025), and the currently available NBT treatments mostly focus on more common cases (e.g., nusinersen for spinal muscular atrophy) (Moultrie et al. 2025). The interdisciplinary team needed for development of such personalized medicines would require members with expertise in diagnosing the diseases, sequencing the mutations, designing and manufacturing NBTs to pharmaceutical standards, resolving patent issues, ensuring regulatory compliance, and administering the treatmentwith all of this provided in time to stop the progression of the disease. Assembling such a team for each individual case in limited available time is practically impossible under current conditions. This process however could be facilitated if there were institutions providing the necessary infrastructure, such as organizations capable of all the above functions.Establishing and financing such institutions represents probably the biggest challenge in translation of achievements in personalized medicine to the clinic. Other problems in this case include the need for regulatory bodies to develop the appropriate framework for personalized drugs and maintain specialized personnel for inspections, as well as multiple other legal and societal implications including treatment cost, patent issues, and ethical considerations.Senti et al. propose the NANOSPRESSO project as a solution to the challenges posed by translation of personalized NBTs to the clinic (Senti et al. 2025). NANOSPRESSO promotes decentralized personalized production of formulated NBTs, construed as drugs for magistral preparation in hospital pharmacies. Magistral preparation is used for individual patients when no approved alternatives exist, which is the case in many rare diseases.Senti et al. outline a production protocol that includes encapsulation of NBTs in lipid nanoparticles (LNPs) using microfluidics technology on location at hospital pharmacies. The NBTs will have to be custom-designed for individual patients, or small groups of patients.This could represent the most labor-intensive, unpredictable, and expensive step in the production process. The designed NBTs will then be manufactured at pharmaceutical-grade nucleic acid synthesis facilities (potentially including CelluTx LLC, siTOOLs Biotech, or Anjarium Biosciences AG). The authors envision that the final step of NBT drug manufacture, its encapsulation in LNPs (potentially designed and manufactured by companies such as Lipoid or NanoVation Therapeutics), will be accomplished at the hospital pharmacies using a specialized piece of microfluidics equipment (potentially by Solstice Act (FDCA) exempts pharmacy compounding performed for a specific patient from FDCA requirements such as compliance with current good manufacturing practices (cGMP), appropriate labeling, and US Food and Drug Administration (FDA) approval. However, due to complex and innovative nature of NBTs the regulatory bodies may need to develop the appropriate framework for personalized NBTs and maintain purpose-trained personnel for routine inspections of facilities in hospital pharmacies. Importantly, the authors stress their on-going communication with European and state regulatory authorities (Senti et al. 2025).Notably, the NANOSPRESSO project considers the implications of the patent laws, ethical considerations around gene editing and the implications for social equity and human diversity, all of which are essential for the wide adoption of personalized NBTs. Notably, the NANOSPRESSO project also plans to develop a unified platform for technology and data sharing with blockchain security and consistent data formats across the network. Such platform can ensure patient privacy and intellectual property protection and provide easy interface with AI tools.The current NANOSPRESSO-NL project is supported by a Netherlands Science Agenda-Netherlands Organization for Scientific Research grant. However, it is only a 6-year project, which does not allow sufficient time given the scope of the undertaking. Other financing sources may be available. Notably, the potential market for personalized drug technology is substantial, as more than 300 million people worldwide suffer from genetic disorders (The Lancet Global Health, 2024, Cavaller-Bellaubi et al. 2023). Additionally, new genetic disease-and cancer-causing mutations are discovered every year. From the reimbursement point of view, treatment with NBTs could significantly decrease lifelong spending compared to the currently available treatments. For example, average inpatient admission costs over a 12 month period post treatment with nusinersen (an NBT for spinal muscular atrophy (SMA))were reduced by 63% in pediatric patients and by 79% in adult patients as compared to the 12 months pre-nusinersen treatment with prior standard care (Zhu et al. 2024). Treatment with single injection gene therapy drug for SMA, onasemnogene abeparvovec, further reduced the annual numbers of inpatient admissions (by 66%) and emergency department visits (by 50%) compared to nusinersen treatment (Toro et al. 2023). These numbers are especially significant given that direct non-healthcare informal cost for families of SMA patients can reach 63% of total annual disease cost (Landfeldt et al. 2023;LĂłpez-Bastida et al. 2017).Experience gained in the NANOSPRESSO project may help obtain a more realistic estimate of the benefits afforded by personalized drugs.Furthermore, data and expertise gained in the treatment of rare diseases could be instrumental in developing drugs for common diseases. The 'intervention-outcome' type datasets in uniform format generated by NANOSPRESSO could be essential for training AI tools for discovery of novel gene-disease associations, structure-activity relationships, assessing delivery efficiency of the LNP formulations and toxicity of NBTs, etc. Reports on drug preparation procedures and treatment outcomes provided by clinics utilizing the NANOSPRESSO approach are likely to be an important asset generated by the NANOSPRESSO program. Licensing access to data and reports generated in the NANOSPRESSO project to pharmaceutical and biotechnology companies could provide revenue to extend the project beyond the current 6-year funding period. However, fundraising (and associated expenses) may be needed to engage these and other financing sources, including rare disease foundations, charitable organizations, and government programs.At present the NBT treatments might not lead to a complete cure, due to late diagnoses, incomplete knowledge of disease biology, poor delivery to target tissues, suboptimal dosing regimens, toxicity, immunogenicity, etc. However, these issues can be resolved with more experience using NBTs in the clinic. Importantly, even in their current form, NBTs can bring significant improvements in patients' and caregivers' quality of life and relief to the financial burden (Zhu et. al 2024, Toro et al. 2023).As significant as the challenges with magistral production of personalized fNBTs are, they are surmountable given the measures proposed by NANOSPRESSO. Furthermore, as Senti et al. point out, there are successful precedents of personalized technologies being used at the point of care, e.g., the Prodigy system (Miltenyi Biotec, Inc) that automated the entire process of chimeric antigen receptor (CAR)-T cell manufacturing from cell activation to reinfusion.The NANOSPRESSO project could also tap into a pro-active network of rare disease foundations. Notably, NANOSPRESSO could enhance community participation by improving their website and posting frequent updates on the project plans, progress, crowdsourcing efforts and citizen scientists' initiatives, as the website could be the project's
Don Husereau, Terrence Sullivan, Harriet Feilotter, Marcio M. Gomes · 9 authors
AIMS: The Canadian province of Ontario provides full coverage for its residents (pop.14.8 M) for hospital-based diagnostic testing. Historical governance of the healthcare system and a legacy scheme of health technology assessment (HTA) and financing has led to a suboptimal approach of adopting advanced diagnostic technology (i.e. protein expression, cytogenetic, and molecular/genetic) for guiding therapeutic decisions. The aim of this research is to explore systemic barriers and provide guidance to improve patient and care provider experiences by reducing delays and inequity of access to testing, while benefitting laboratory innovators and maximizing system efficiency. MATERIALS AND METHODS: = 2). The forum considered evidence of good practices in adoption, implementation, and financing laboratory services and identified barriers as well as feasible options for improving advanced diagnostic testing in Ontario. RESULTS: Overarching challenges identified included: barriers to define what is needed; need for a clear approach to adoption; and the need for more oversight and coordination. Recommendations to address these included a shift to an anticipatory system of test adoption, creating a fit-for-purpose system of health technology management that consolidates existing evaluation processes, and modernizing the governance and financing of testing so that it is managed at a care-delivery level. CONCLUSIONS: The proposals for change in Ontario highlight the role that HTA, governance, and financing of health technology play along the continuum of a health technology life cycle within a healthcare system where decision-making is highly decentralized. Resource availability and capacity were not a concern - instead, solutions require higher levels of coordination and system integration along with innovative approaches to HTA.
Open access
Health Systems, Economic Evaluations, Quality of Life
Patrick Silva, Deborah Vollmer Dahlke, Matthew Lee Smith, Wendy Charles · 7 authors
Current best practices in tumor registries provide a glimpse into a limited time frame over the natural history of disease, usually a narrow window around diagnosis and biopsy. This creates challenges meeting public health and healthcare reimbursement policies that increasingly require robust documentation of long-term clinical trajectories, quality of life, and health economics outcomes. These challenges are amplified for underrepresented minority (URM) and other disadvantaged populations, who tend to view the institution of clinical research with skepticism. Participation gaps leave such populations underrepresented in clinical research and, importantly, in policy decisions about treatment choices and reimbursement, thus further augmenting health, social, and economic disparities. Cloud computing, mobile computing, digital ledgers, tokenization, and artificial intelligence technologies are powerful tools that promise to enhance longitudinal patient engagement across the natural history of disease. These tools also promise to enhance engagement by giving participants agency over their data and addressing a major impediment to research participation. This will only occur if these tools are available for use with all patients. Distributed ledger technologies (specifically blockchain) converge these tools and offer a significant element of trust that can be used to engage URM populations more substantively in clinical research. This is a crucial step toward linking composite cohorts for training and optimization of the artificial intelligence tools for enhancing public health in the future. The parameters of an idealized clinical genomic registry are presented.
Marco Piccininni, Jessica L. Rohmann, Giancarlo Logroscino, Tobias Kurth
Rare diseases are difficult if not impossible to study outside of population-based registries. Particularly in the context of rare neurodegenerative diseases characterized by case heterogeneity, difficult differential diagnosis by specialists and small numbers of patients, registries make otherwise unfeasible incidence studies cost-effective and manageable. Building up and maintaining such registries is challenging and requires strong, active and collaborative networks. Centralization around a leading institution provides structure and consistency, but this single-site storage leads to inefficiency and bottlenecks and is prone to failures, attacks, and manipulation. Furthermore, a substantial amount of trust is required between parties sharing data in a traditional registry. Patients are increasingly reluctant to share data with regular news reports about healthcare data breaches and underfunded rare disease specialists are also hesitant to exchange with the leading institution out of fear that the low numbers of patients may seek treatment elsewhere. A lack of electronic health records and information system interoperability in certain settings leads to information silos and only further exacerbate the other issues. Blockchain technology may provide unique, innovative solutions to many of these challenges. Specifically, through digital trust and the use of an immutable distributed ledger, automated data transaction processing, guaranteed integrity, enhanced security, blockchain technology seems to be perfectly suitable to optimize current population-based rare neurodegenerative disease registry construction and maintenance.
Gamze GĂŒrsoy, Charlotte M. Brannon, Mark Gerstein
Abstract Background With the advent of precision medicine, pharmacogenomics data is becoming increasingly critical to patient care. These data describe the relationship between a particular variant in the genome and the response to a drug by the patient. As utilizing this kind of data becomes more integral to medical treatment decisions, appropriate storage and sharing of this data will be critical. A potential way of securely storing and sharing pharmacogenomics data is a smart contract with the Ethereum blockchain. This is an open-source blockchain platform for decentralized applications. A transaction-based, state machine, the âworldâ of Ethereum maintains user accounts and storage in a network state. Immutable pieces of code called âsmart contractsâ may be deployed to the Ethereum network and run on the Ethereum Virtual Machine when called by a user or other contract. The 2019 iDASH (Integrating Data for Analysis, Anonymization, and Sharing) competition for Secure Genome Analysis challenged participants to develop time- and space-efficient smart contracts to log and query gene-drug relationship data on the Ethereum blockchain. Methods We designed a smart contract to store and query pharmacogenomics data (gene-drug interaction data) in Ethereum using an index-based, multi-mapping approach allowing for time and space efficient storage and query. Our solution to the IDASH competition ranked in the top three at a workshop held in Bloomington, IN in October 2019. Although our solution performed well in the challenge, we wanted to improve its scalability and query efficiency. To that end, we developed an alternate âfastQueryâ solution that stores pooled rather than raw data, allowing for significantly improved query time for 0-AND queries, and constant query time for 1- and 2-AND queries. Results We tested the performance of both of our solutions in Truffle (v5.0.31) using datasets ranging from 100 to 1000 entries, and inserting data at 25, 50, 100, and 200 observations at a time. On a private, proof-of-authority test network, our challenge solution requires approximately 70 seconds, 500 MB of memory, and 80 MB of disk space to insert 1000 entries (200 at a time); and 400 ms and 5 MB of memory to query a two-AND query from 1000 entries. This solution exhibits constant memory for insertion and querying, and linear query time. Our alternate fastQuery solution requires approximately 60 seconds, 500 MB of memory, and 80 MB of disk space to insert 1000 entries (200 at a time); and 83 ms and 5 MB of memory to query a two-AND query from 1000 entries. This solution exhibits constant memory for insertion and querying, linear query time for 0-AND queries, and constant query time for 1- and 2-AND queries in a database of up to 1000 entries. Conclusion In this study we showed that pharmacogenomics data can be stored and queried efficiently on the Ethereum blockchain. Our approach has the potential to be useful for a wide range of datasets in biomedical research; while we focused on gene-drug interaction data, our solution designs could be used to store a range of clinical trial data. Moreover, our solutions could be adapted to store and query data in any field where high-integrity data storage and efficient access is required.
Eric Venner, Mullai Murugan, Walker Hale, Jordan M Jones · 7 authors
MOTIVATION: Clinical genome sequencing laboratories return reports containing clinical testing results, signed by a board-certified clinical geneticist, to the ordering physician. This report is often a PDF, but can also be a paper copy or a structured data file. The reports are frequently modified and reissued due to changes in variant interpretation or clinical attributes. MATERIALS AND METHODS: To precisely track report authenticity, we developed ARBoR (Authenticated Resources in a Hashed Block Registry), an application for tracking the authenticity and lineage of versioned clinical reports even when they are distributed as PDF or paper copies. ARBoR tracks clinical reports as cryptographically signed hash blocks in an electronic ledger file, which is then exactly replicated to many clients. RESULTS: ARBoR was implemented for clinical reporting in the Human Genome Sequencing Center Clinical Laboratory, initially as part of the National Institute of Health's Electronic Medical Record and Genomics (eMERGE) project. CONCLUSIONS: To date, we have issued 15 205 versioned clinical reports tracked by ARBoR. This system has provided us with a simple and tamper-proof mechanism for tracking clinical reports with a complicated update history.