Delivery Engineering for Genome Editors: Viral and Non-Viral Vectors, Biomaterials, and Physical Delivery
Genome editing is advancing at a rapid pace, but efficient, safe, and targeted delivery remains one of the main barriers to translation. Editing modalities—including CRISPR–Cas nucleases, base editors, prime editors, and emerging RNA-guided systems—require delivery solutions that balance potency with tissue specificity, manufacturability, and acceptable safety profiles. At the same time, the field is moving beyond “one-size-fits-all” approaches toward rational delivery engineering tailored to editor format (DNA, mRNA, RNP), target tissue, dosing needs, and clinical context.This Research Topic focuses on delivery engineering strategies for genome editors, spanning viral and non-viral vectors, biomaterials-based carriers, and physical delivery methods. We welcome work on viral delivery systems (e.g., AAV, adenovirus, lentiviral/retroviral vectors, HSV and other emerging viral platforms) alongside lipid nanoparticles (LNPs), virus-like particles (VLPs), polymer-based systems, and device-enabled approaches. Submissions that advance the design, characterization, and translation of delivery platforms—including strategies to improve targeting, control biodistribution, enhance intracellular trafficking/endosomal escape, reduce immunogenicity, manage duration of editor exposure, and enable repeat dosing—are especially encouraged. Studies that compare platforms head-to-head, develop predictive assays, or establish scalable manufacturing and quality frameworks are also strongly encouraged.Topics of interest include (but are not limited to):1. Viral vector engineering: AAV capsid and genome design, tropism retargeting, payload constraints and split editor strategies, promoter/regulatory element design, transient vs durable expression, integration risk and genotoxicity considerations, immunogenicity and redosing, and next-generation viral platforms2. LNP engineering: ionizable lipid design, formulation optimization, targeting ligands, endosomal escape, organ-selective delivery, and durability of editing3. VLP-based delivery: capsid engineering, payload loading, tropism control, repeat dosing, and immune evasion strategies4. Polymeric and hybrid carriers: biodegradable polymers, stimuli-responsive materials, charge/architecture tuning, polymer–lipid hybrids, and safety considerations5. Physical delivery approaches: electroporation, microfluidics, hydrodynamic delivery, ultrasound-mediated delivery, microneedles, and other device-enabled methods6. Cargo formats and packaging: DNA vs mRNA vs RNP delivery, multiplex editing, co-delivery (e.g., editor + guide + donor), and dose/exposure control7. In vivo and ex vivo translation: delivery to difficult tissues (e.g., CNS, lung, muscle), cell therapy workflows, and process development8. Preclinical evaluation: biodistribution, pharmacokinetics/pharmacodynamics, off-target assessment, immunogenicity, toxicity, and durability9. Manufacturing and regulatory-enabling studies: scalability, analytics, stability, reproducibility, and quality-by-design across viral and non-viral systems Topic editors: Purusottam Mishra, Meysam Ganjibakhsh, Amit Kumar Srivastava, Manuel Reithofer Source: https://www.frontiersin.org/research-topics/77664/delivery-engineering-for-genome-editors-viral-and-non-viral-vectors-biomaterials-and-physical-delivery
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