Advances in base editing with an emphasis on an AAV-based strategy

Area of Science:

• Genetics and Genomics
• Molecular Biology
• Biotechnology

Background:

• CRISPR-based base editors enable precise point mutation installation.
• Cytosine base editors (CBEs) convert C•G to T•A, and Adenine base editors (ABEs) convert A•T to G•C.
• These editors are crucial for genomic DNA correction and mutation introduction.

Purpose of the Study:

• To summarize recent optimizations in CRISPR base editor technology.
• To highlight split-intein mediated base editor reconstitution for adeno-associated virus (AAV) delivery.
• To facilitate the use of AAV-mediated base editors in in vivo experiments and clinical applications.

Main Methods:

• Review of evolved Cas proteins and deamination enzymes.
• Analysis of linker length modifications and base editor expression strategies.
• Exploration of functional domain additions and split-intein mediated reconstitution.

Main Results:

• Optimized base editors show improved efficiency and specificity.
• Split-intein systems facilitate AAV-mediated delivery of base editors.
• Various strategies enhance base editor performance for genomic applications.

Conclusions:

• CRISPR base editors are powerful tools for precise genome editing.
• Optimizations enhance base editor utility for in vivo applications.
• AAV-mediated delivery systems are promising for clinical translation.