DeCure for Recombinase activating gene 1 deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for recombinase activating gene 1 deficiency — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleRecombinase activating gene 1 deficiency maps to a 1-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for recombinase activating gene 1 deficiency is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
What the evidence adds up to
Gene therapy for severe combined immunodeficiency, the broader category that includes recombinase activating gene 1 deficiency, has produced immune reconstitution in most treated patients in gammaretroviral trials, but a minority derived minimal benefit and some suffered severe adverse events including death. Insertion site analyses from trials for X-linked SCID, adenosine deaminase-deficient SCID and chronic granulomatous disease found preferential vector insertion near the 5' ends of genes, including proto-oncogenes and signal transduction and proliferation genes, which is the mechanism behind the observed leukaemias. Preclinical work in rodents and canines has tested lentiviral and foamy viral vectors to reduce this genotoxicity, but no clinical data from those newer vectors are presented in these abstracts.
Site-specific recombinases derived from yeast—KD, B2, B3 and R—were shown to be highly active and nontoxic in Drosophila, with KD, B2, B3 and FLP having distinct target specificities, and KD and B3 were active in mice. These recombinases are tools for manipulating animal genomes and for lineage tracing, not therapeutic agents for RAG1 deficiency. Dual-recombinase systems improve genetic resolution in lineage tracing compared with single-recombinase approaches, but this is a laboratory technique for studying cell fate, not a treatment.
A 2025 review of gene therapy in childhood disease states that gene transfer to the haematopoietic compartment has provided the clearest examples of therapeutic benefit in primary immunodeficiencies, but the same review's own results section is largely promotional, claiming gene therapy could eliminate AIDS, malignancies and hereditary disorders, with no supporting data given. The abstracts contain no clinical trial results specific to RAG1 deficiency, no patient numbers for that condition, and no survival or response-rate figures for any recombinase-based approach.
What is missing is any direct clinical evidence for RAG1 deficiency: no trial size, no follow-up duration, no stratification by residual RAG1 activity or age at treatment, and no comparison of lentiviral versus gammaretroviral outcomes in this specific disease. The financial and regulatory infrastructure for a dedicated RAG1 trial, including long-term monitoring for insertional mutagenesis, is also absent from these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Proceedings of the National Academy of Sciences · 2011 · 181 citations · open access
Multiple new site-specific recombinases for use in manipulating animal genomes
AbstractSite-specific recombinases have been used for two decades to manipulate the structure of animal genomes in highly predictable ways and have become major research tools. However, the small number of recombinases demonstrated to have distinct specificities, low toxicity, and sufficient activity to drive reactions to completion in animals has been a limitation. In this report we show that four recombinases derived from yeast--KD, B2, B3, and R--are highly active and nontoxic in Drosophila and that KD, B2, B3, and the widely used FLP recombinase have distinct target specificities. We also show that the KD and B3 recombinases are active in mice.
Current Opinion in Hematology · 2008 · 40 citations · open access
Recent advances in gene therapy for severe congenital immunodeficiency diseases
AbstractPURPOSE OF REVIEW: To discuss new data on the safety and efficacy of the ongoing gene therapy trials for primary immune deficiencies, the first reports of new trials and the preclinical developments that are likely to be translated to the clinic in the near future. RECENT FINDINGS: Both clinical successes and severe adverse events continue to be reported in trials of gammaretroviral gene therapy for severe combined immune deficiency-X1, adenosine deaminase-deficient forms of severe combined immune deficiency and chronic granulomatous disease. Insertion site analyses of recently reported trials on all of these diseases have discovered preferential insertion in the 5' ends of genes, including potentially dangerous ones such as proto-oncogenes and signal transduction and proliferation genes. Preclinical work on rodent and canine models has tested novel vectors, including lentiviruses and foamy viruses. SUMMARY: Gene therapy for the most common forms of severe combined immune deficiency can lead to immune reconstitution in most patients, although a minority of patients has derived minimal clinical benefit and some have suffered severe adverse events including death. Ongoing preclinical work attempts to address the latter shortcoming. Meanwhile, in the presence of a careful risk-benefit assessment, gene therapy remains an appropriate subject of clinical investigation.
AbstractAs a powerful genetic tool, site-specific recombinases (SSRs) have been widely used in genomic manipulation to elucidate cell fate plasticity in vivo, advancing research in stem cell and regeneration medicine. However, the low resolution of conventional single-recombinase-mediated lineage tracing strategies, which rely heavily on the specificity of one marker gene, has led to controversial conclusions in many scientific questions. Therefore, different SSRs systems are combined to improve the accuracy of lineage tracing. Here we review the recent advances in dual-recombinase-mediated genetic approaches, including the development of novel genetic recombination technologies and their applications in cell differentiation, proliferation, and genetic manipulation. In comparison with the single-recombinase system, we also discuss the advantages of dual-genetic strategies in solving scientific issues as well as their technical limitations.
GSC Biological and Pharmaceutical Sciences · 2025 · 0 citations · open access
Gene therapy: A progress in childhood disease
AbstractAs gene therapy is one of the hottest topics of the new century, it carries the excitement of a cure to most of dis controversy surrounding the altering of human imperfection, and the promise of a type of medical treatment most of cause would never imagine possible The recent sequence of the human genome combined with the development of massively high throughput genetic analysis technologies is driving unprecedented growth in knowledge of the molecular basis of disease. While this has already had a major function in our diagnostic power, the therapeutic benefits remain largely unrealized. This review examines progress in the exciting and challenging form of gene therapy, in particular we focus on the treatment of genetic disease in infants and children where the most significant successes have been observed to date, despite the majority of total participants coming from adults. Notably, gene transfer to the haematopoietic compartment has provided the clearest examples of therapeutic benefit, particularly in the context of primary immunodeficiencies. (1) Material and methods: A thorough search of literature carried out through the National library of medicine (PubMed), SCOPUS, EMBASE databases using different Keywords. All the relevant articles were analyzed according to their importance And reviewed to evaluate the past present and future perspective of gene therapy. Resalty: With a possibility to eliminate and present AIDS, malignancies, hereditary disorders and it's conceivable cure for cardiac disorders, gene therapy is nothing short of a medical phenomenon. (1)
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
