Biology subjects

Macfarlane, R. J.

Publications and source records attributed to Macfarlane, R. J..

3 recordsLinked to original sources

bioRxiv2026

CHARIOT-AAV: Conjugation of diverse vectors to adeno-associated viruses for delivery of large genes

Systemic, tissue-specific delivery of large transgenes exceeding the packaging capacity of adeno-associated viruses (AAVs) remains a key translational challenge for molecular therapeutics. Vectors with larger capacities, such as lentiviral vectors (LVVs) and lipid nanoparticles (LNPs), often lack adjustable, tissue-specific tropisms. Here we report CHARIOT-AAV (Crosslinked Hybrid Architectures for Robust, Interchangeable, and Organ-specific Targeting with AAV), a platform where diverse delivery vectors are conjugated to AAVs, thereby achieving tissue-specific tropism of AAVs and expanded cargo capacity. AAV-AAV conjugates packaging split SpCas9 constructs in AAV.CAP-B10 capsids demonstrate a [~]2-fold increase in brain gene editing efficiency over unconjugated AAV cocktails after intravenous injection. In addition to AAV-AAV conjugates, AAV-LVV and AAV-LNP conjugates achieve AAV-guided delivery of genetic payloads to target cells. Furthermore, AAV-LNP conjugates enable systemic delivery of mRNAs to brain endothelial cells. CHARIOT-AAV thus provides a modular platform for systemic, tissue-specific delivery of diverse therapeutics beyond the limits of individual vectors.

bioengineering↗

bioRxiv2025

Adeno-associated viruses escort nanomaterials to specific cells and tissues

The delivery of nanotherapeutics to specific tissues relies on bespoke targeting strategies or invasive surgeries. Conversely, adeno-associated viruses (AAVs) can target specific tissues following intravenous injections. Here we show that cell-targeting properties of AAVs could be broadly conferred to nanomaterials. We develop a strategy to couple AAV capsids to nanoparticles that is invariant of viral serotype or nanomaterial chemistry and permits control over stoichiometry of the AAV-nanoparticle chimeras. The chimeras selectively escort nanoparticles into cell classes governed by AAV serotypes. When applied to magnetic nanoparticles, the AAV-nanoparticle chimeras enable magnetically localized gene delivery. In vivo, we show that leveraging the brain-targeting AAV serotype CAP-B10 achieves nanoparticle delivery to the parenchyma with [~]10% efficiency (% injected dose/g[brain]) while avoiding accumulation in the liver. The enhanced delivery efficiency and tissue specificity highlight the potential of AAV-chimeras as a versatile strategy to escort broad classes of nanotherapeutics to the brain and beyond.

bioengineering↗

bioRxiv2025

DNA origami directed integration of colloidal nanophotonic materials with silicon photonics

Incorporation of colloidal quantum emitters into silicon-based photonic devices would enable major advances in quantum optics. However, deterministic placement of individual sub-10 nm colloidal particles onto micron-sized photonic structures with nanometer-scale precision remains an outstanding challenge. Here, we introduce Cavity-Shape Modulated Origami Placement (CSMOP) that leverages the structural programmability of DNA origami to precisely deposit colloidal nanomaterials within lithographically-defined resist cavities. CSMOP enables clean and accurate patterning of origami templates onto photonic chips with high yields. Soft-silicification-passivation stabilizes deposited origamis, while preserving their binding sites to attach and align colloidal quantum rods (QRs) to control their nanoscale positions and emission polarization. We demonstrate QR integration with photonic device structures including waveguides, micro-ring resonators, and bullseye photonic cavities. CSMOP therefore offers a general platform for the integration of colloidal quantum materials into photonic circuits, with broad potential to empower quantum science and technology.

bioengineering↗