Mar 12, 2021 · Our data reveal that the capsids assemble stochastically, leading to a highly heterogeneous population of capsids of variable composition, whereby even the single-most abundant VP stoichiometry...

Adeno-associated virus (AAV) is one of the most promising viral gene transfer vectors that has been shown to effect long-term gene expression and disease correction with low toxicity in animal models, and is well tolerated in human clinical trials.

May 16, 2024 · The top-performing capsid, AAV-BI-hTFR1, exhibited more efficient gene delivery to and improved active transport across human brain endothelial cells. When systemically administered to adult human TFRC knockin (KI) mice, BI-hTFR1 transduced most neurons and astrocytes across multiple brain regions.

Mar 26, 2024 · By swapping the VP1 N terminus from primate AAVs (e.g., AAV8) onto non-mammalian isolates (e.g., avian AAV), we identify a minimal component of the AAV capsid that controls viral transcription and unlocks robust transduction in both human cells and mouse tissue.

Here, we establish an in vivo strategy to evolve and stringently select capsid variants of adeno-associated viruses (AAVs) that enable potent delivery to desired tissues.

In this article, we provide a brief historical account of the progress that has been made in the development of capsid-modified, next-generation AAV vectors to ensure both the safety and efficacy of these vectors in targeting a wide variety of human diseases.

Jan 18, 2025 · Adeno-associated virus (AAV) capsid proteins are pivotal in gene therapy, offering promising avenues for treating genetic disorders. Their unique properties make them ideal vectors for delivering therapeutic genes to target cells with specificity and efficiency.

Dec 9, 2021 · Here we show organ-specific targeting of adeno-associated virus (AAV) capsids after intravenous delivery, which we achieved by employing a Cre-transgenic-based screening platform and...

This chapter reviews the current structural information on AAV capsids and the capsid viral protein regions playing a role in the cellular interactions conferring an infective phenotype, which are then used to annotate the functional regions of the capsid.

Nov 29, 2019 · Adeno-associated virus (AAV) capsids can deliver transformative gene therapies, but our understanding of AAV biology remains incomplete. We generated the complete first-order AAV2 capsid fitness landscape, characterizing all single-codon substitutions, insertions, and deletions across multiple functions relevant for in vivo delivery.