ReviewJournal of hematology & oncology2026
The advances and challenges of mRNA-LNP application in fields of hematology and oncology therapeutics.
Review in Journal of hematology & oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 authors.
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Abstract
The rapidly global deployment of COVID-19 mRNA-LNP vaccines established the clinical feasibility of combining RNA medicine with LNP delivery systems, transforming a long-standing experimental concept into a scalable therapeutic modality, previously considered impossible. Currently, the value of mRNA-LNPs has been expanding from infectious disease vaccines to cancer immunotherapy, personalized neoantigen vaccination, in vivo immune-cell engineering, protein replacement therapy, mRNA-encoded biologics and genome editing, with particular relevance to hematology and oncology. However, in hematologic and oncologic settings, therapeutic success is constrained by biological barriers that less prominent in prophylactic vaccination. Systemically administered LNPs are strongly influenced by hepatic sequestration, protein corona formation and mononuclear-phagocyte clearance; solid tumors additionally present heterogeneous vasculature, variable enhanced permeability and retention, dense extracellular matrix, elevated interstitial pressure and limited intratumoral diffusion. Hematologic applications face a different set of constraints, including access to spleen and bone marrow, selective delivery to T cells, NK cells and hematopoietic stem and progenitor cells (HSPCs), and preservation of the normal marrow niche. In this Review, we therefore discuss the molecular and principles of formulation that underpin mRNA-LNP performance in hematology and oncology, including mRNA engineering, lipid nanoparticle architecture, intracellular trafficking and selective organ targeting(SORT) delivery strategies, oncology applications spanning neoantigen vaccines, tumor-microenvironment reprogramming, mRNA-encoded biologics, gene editing and combination therapy; and hematology applications including in vivo CAR-T, CAR-NK and HSPC engineering. We further consider how inefficient extrahepatic delivery, limited endosomal escape, context-dependent reactogenicity, repeat-dosing constraints and the manufacturing complexity of individualized products continue to limit broader clinical translation. Emerging strategies, including artificial-intelligence-guided RNA and lipid design, self-amplifying RNA, circular RNA and next-generation thermostable formulations, may help address these application limitations in the fields of hematology and oncology.
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Registered trials
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