Systematic multi-trait AAV capsid engineering for efficient gene ...
2024年8月4日 · Here, we present Fit4Function, a generalizable machine learning (ML) approach for systematically engineering multi-trait AAV capsids. By leveraging a capsid library that uniformly samples the...
Engineering adeno-associated virus vectors for gene therapy
2020年2月10日 · In this Review, we discuss how AAV vectors can be genetically engineered to enhance their transduction and production and to overcome immunity barriers in patients. Additionally, we propose how...
AAV capsid variants with brain-wide transgene expression and
2021年12月9日 · 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 sequential...
Computationally guided AAV engineering for enhanced gene …
2024年5月1日 · Adeno-associated virus (AAV) capsid engineering strategies. AAV libraries can be created through various methods, including random diversification techniques, computationally aided design, and the utilization of computational models specifically trained to construct capsids with desired properties.
Capsigen | Driven to Evolve
The next-generation AAV vectors are fueling gene therapy. By combining state-of-the-art knowledge of biology, directed evolution, and data science, Capsigen is engineering novel AAV capsids to address difficult-to-treat diseases.
AAV capsid design: A Goldilocks challenge - ScienceDirect
2022年3月1日 · The adeno-associated virus (AAV) vector manifested itself as a preferred gene delivery vehicle enabling therapeutic gene expression for several clinical indications. Here, we cover the recent trends in AAV capsid engineering to …
Systematic multi-trait AAV capsid engineering for efficient gene ...
2022年12月22日 · Here, we present Fit4Function, a generalizable machine learning (ML) approach for systematically engineering multi-trait AAV capsids. By leveraging a capsid library that evenly samples the manufacturable sequence space, reproducible screening data are generated to train accurate sequence-to-function models.
Non-canonical capsid engineering highlights new possibilities for AAV …
In the described paper, Chang and colleagues report potential benefits of incorporating non-canonical amino acids (ncAAs) into AAV capsid proteins to modify their activity.
Comprehensive AAV capsid fitness landscape reveals a viral ... - Science
2019年11月29日 · 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.
Capsid Modifications for Targeting and Improving the Efficacy of AAV …
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.
An AAV capsid reprogrammed to bind human transferrin receptor …
2024年5月16日 · We engineered an adeno-associated virus (AAV) capsid, BI-hTFR1, that binds human transferrin receptor (TfR1), a protein expressed on the blood-brain barrier. BI-hTFR1 was actively transported across human brain endothelial cells and, relative to AAV9, provided 40 to 50 times greater reporter expression in the CNS of human TFRC knockin mice.
AAV capsid design: A Goldilocks challenge - PubMed
The adeno-associated virus (AAV) vector manifested itself as a preferred gene delivery vehicle enabling therapeutic gene expression for several clinical indications. Here, we cover the recent trends in AAV capsid engineering to enhance its targeting specificity, safety, and endurance.
Engineering viral vectors for acoustically targeted gene delivery
2024年6月10日 · To identify new AAV variants with improved FUS-BBBO-targeted transduction of neurons, we generated a library of viral capsid sequences containing insertions of 7 randomized amino acids between...
Directed evolution of a family of AAV capsid variants enabling …
In summary, we report here the evolution, engineering, and mechanistic characterization of a family of highly potent muscle-directed AAV capsid variants across species. We demonstrate these vectors’ therapeutic efficacy, even at low dosage, in multiple mouse models of genetic muscle disease.
AAV capsid design: A Goldilocks challenge - Cell Press
2022年1月26日 · The adeno-associated virus (AAV) vector manifested itself as a preferred gene delivery vehicle enabling therapeutic gene expression for several clinical indications. Here, we cover the recent trends in AAV capsid engineering to …
Machine-learning-guided Directed Evolution for AAV Capsid Engineering ...
2024年3月5日 · Artificial intelligence (AI), especially machine learning (ML), has great potential to accelerate and improve the optimization of capsid properties as well as decrease their development time and manufacturing costs.
Structure-guided AAV capsid evolution strategies for enhanced …
2023年9月21日 · Over the past 5 years, our laboratory has systematically developed a structure-guided library approach to evolve new adeno-associated virus (AAV) capsids with altered tissue tropism, higher...
Genome engineering with Cas9 and AAV repair templates
2025年1月13日 · Genome editing, in particular the CRISPR/Cas9 system, is widely used to generate new animal models. However, the generation of mutations, such as conditional knock-out or knock-in, can remain complex and inefficient, in particular because of the difficulty to deliver the donor DNA (single or double stranded) into the nucleus of fertilized oocytes. The use of …
Modifying immune responses to adeno-associated virus vectors by capsid …
2023年9月14日 · With the aim to lower innate immune responses directly in cells targeted by adeno-associated virus (AAV) vectors, we equipped the vector capsid with a peptide known to interfere with Toll-like receptor signaling.
Towards a Platform Chromatography Purification Process for …
2025年1月16日 · Adeno-associated virus (AAV) is a versatile viral vector technology that can be engineered for specific functionality in vaccine and gene therapy applications. One of the major challenges in AAV production is the need for a GMP-ready platform-based approach to downstream processing, as this would lead to a standardized method for multiple products.
Scratching the surface of RGD-directed AAV capsid engineering
2021年11月3日 · Tabebordbar et al. 2 describe isolation of AAV capsid variants efficiently targeting muscle in mice and NHPs. These new capsid variants were derived through the process of directed evolution (DE) of combinatorial capsid libraries built upon an AAV9 capsid scaffold.
Adeno-associated virus capsid assembly is divergent and stochastic - Nature
2021年3月12日 · Adeno-associated viruses (AAVs) are increasingly used as gene therapy vectors. AAVs package their genome in a non-enveloped T = 1 icosahedral capsid of ~3.8 megaDalton, consisting of 60...
Liver-avoiding capsids draw $1.1 billion | Nature Biotechnology
2025年1月17日 · Kate’s platform approach for engineering RGD-modified AAVs — known as DELIVER: directed evolution of AAV capsids leveraging in vivo expression of transgene RNA — can be used for any tissue type.
Co-delivery of IL-1Ra and SOX9 via AAV inhibits inflammation and ...
4 天之前 · AAVJ4 was the candidate joint-tropic AAV capsid for KOA gene therapy. Four capsids, AAVJ1, AAVJ2, AAVJ3, and AAVJ4 were selected from an AAV capsid gene shuffled library as described before [].The ...