AAV-vectored base editor trans-splicing delivers dystrophin repair

Review Biotechnology & Applied Microbiology

Progress in Bioengineering of Myotropic Adeno-Associated Viral Gene Therapy Vectors

Jixin Liu et al.

Summary: The ability to transfer therapeutic payloads to specific muscles in a safe and efficient manner through a minimally invasive route is a crucial goal in human gene therapy. Recombinant adeno-associated viruses (AAVs) have been extensively used for this purpose, either delivering cargoes in various wild-type capsids or synthetic protein shells. This study provides an overview of commonly used techniques to enrich muscle-specific AAV capsids, including genetic diversification, stratification of capsid libraries, and alternative strategies such as ancestral reconstruction or rational design. Recent advancements have led to the discovery of myotropic vectors with unprecedented in vivo efficiency and specificity in striated muscles. Future improvements include optimal translation in humans and minimizing off-target effects.

HUMAN GENE THERAPY (2023)

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Article Medicine, Research & Experimental

Single-swap editing for the correction of common Duchenne muscular dystrophy mutations

Andreas C. Chai et al.

MOLECULAR THERAPY-NUCLEIC ACIDS (2023)

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Article Engineering, Biomedical

Efficient in vivo base editing via single adeno-associated viruses with size-optimized genomes encoding compact adenine base editors

Jessie R. Davis et al.

Summary: Compact adenine base editors (ABEs) encoded within size-optimized genomes of adeno-associated viruses (AAVs) enable therapeutic base editing in mice at low doses and high editing efficiencies, simplifying AAV production and characterization.

NATURE BIOMEDICAL ENGINEERING (2022)

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Review Biotechnology & Applied Microbiology

CRISPR technologies for the treatment of Duchenne muscular dystrophy

Eunyoung Choi et al.

Summary: The CRISPR-Cas system shows potential in treating Duchenne muscular dystrophy (DMD), but challenges in developing more efficient therapeutic approaches and delivery methods remain.

MOLECULAR THERAPY (2021)

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Article Multidisciplinary Sciences

Precise correction of Duchenne muscular dystrophy exon deletion mutations by base and prime editing

F. Chemello et al.

Summary: This study demonstrated the use of adenine base editor to restore dystrophin expression in cardiomyocytes affected by Duchenne muscular dystrophy mutation, as well as reframing the dystrophin open reading frame. In vivo experiments with mice showed successful gene editing and disease correction, indicating the potential of nucleotide editing for diverse DMD mutations with minimal genome modification.

SCIENCE ADVANCES (2021)

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Article Multidisciplinary Sciences

Efficient precise in vivo base editing in adult dystrophic mice

Li Xu et al.

Summary: Recent advances in base editing have allowed for precise correction of disease-causing mutations, but challenges remain in terms of the size of base editors and their off-target activities, as well as the requirement for a specific protospacer adjacent motif (PAM) nearby the mutation site. This study successfully modified an NG-targeting adenine base editor to overcome these challenges and demonstrated its high efficiency in editing a Duchenne muscular dystrophy (DMD) mutation in adult mice, showing promising results with systemic delivery. The authors' approach shows potential for the treatment of monogenic diseases using base editing techniques, addressing limitations in targeting feasibility and packaging capacity.

NATURE COMMUNICATIONS (2021)

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Article Biotechnology & Applied Microbiology