ArticleScience (New York, N.Y.)2019
Comprehensive AAV capsid fitness landscape reveals a viral gene and enables machine-guided design.
Article in Science (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 228 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
228 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Changing trends in the development of AAV-based gene therapies: a meta-analysis of past and present therapies.Gene therapy · 2023Pooled it
- AI-engineered AAV capsid enables intravitreal delivery for the treatment of diverse retinal degenerations.Molecular therapy. Advances · 2026Article
- Scanning the horizon: deep mutational scanning approaches in virology.Journal of virology · 2026Review
- Natural and evolved membrane-associated accessory proteins differentially engage SNARE machinery for AAV egress.Journal of virology · 2026Article
- Epigenetic editing approaches maturity: AI-driven precision design, delivery innovation, and the road to clinical translation.Clinical epigenetics · 2026Review
- Article
- Artificial intelligence in biologic drug discovery: A review of methodological evolution and therapeutic applications.Acta pharmaceutica Sinica. B · 2026Review
- Review
- How far can you go? Extrapolating values of catalytic activity from known protein landscapes in natural and directed evolution.Chemical Society reviews · 2026Review
- Exploring the limits of pre-trained embeddings in machine-guided protein design: a case study on predicting AAV vector viability.Scientific reports · 2026Article
- The adeno-associated virus Rep proteins target PP4:SMEK1 by preventing substrate recruitment.PLoS pathogens · 2026Article
- Rethinking Nature's Pharmacy: AI Era and Natural Product Drug Discovery.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Review
- In vivo engineering of CAR-T cells: delivery strategies and clinical translation.Biomarker research · 2026Review
- Review
- AAV Capsid Modification and Its Influence on Viral Protein Stoichiometry and Packaging Fitness: Current Understandings and Future Direction.Molecular biotechnology · 2026Review
- Engineering of High-Yield Recombinant Adeno-Associated Virus Producer Plasmids.Biotechnology journal · 2026Article
- The delivery challenge of adeno-associated virus vector-based gene therapies for neurological diseases.Frontiers in neuroscience · 2026Review
- Species barriers in AAV tropism: mechanisms, models, and emerging solutions for clinical translation.Acta biochimica Polonica · 2026Review
- Intelligent design of tumor microenvironment-responsive Adeno-associated virus vectors: overcoming delivery barriers and enabling precision therapy.Medical oncology (Northwood, London, England) · 2025Review
168 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
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. We discovered a frameshifted gene in the VP1 region that expresses a membrane-associated accessory protein that limits AAV production through competitive exclusion. Mutant biodistribution revealed the importance of both surface-exposed and buried residues, with a few phenotypic profiles characterizing most variants. Finally, we algorithmically designed and experimentally verified a diverse in vivo targeted capsid library with viability far exceeding random mutagenesis approaches. These results demonstrate the power of systematic mutagenesis for deciphering complex genomes and the potential of empirical machine-guided protein engineering.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.