Base editors: development and applications in biomedicine

Area of Science:

• Molecular Biology
• Biotechnology
• Genetics

Background:

• Base editors (BEs) combine CRISPR/Cas with deaminases for precise DNA/RNA base substitution.
• BEs avoid double-strand breaks (DSBs) and donor DNA, unlike CRISPR/Cas9, reducing genomic damage.
• BEs have significant biomedical applications, including gene function studies, disease modeling, and gene therapy.

Purpose of the Study:

• To review recent advancements in base editor technology.
• To summarize the diverse applications of base editors in biomedicine.
• To discuss future prospects and challenges for therapeutic uses of base editors.

Main Methods:

• Review of scientific literature on base editor development and applications.
• Analysis of base editor mechanisms, including cytosine base editors (CBEs) and adenine base editors (ABEs).
• Summary of over 100 optimized base editor variants and their characteristics.

Main Results:

• Base editors enable precise single-base substitutions without DSBs.
• Over 100 optimized base editors have been developed, enhancing efficiency, precision, and targeting.
• BEs show broad applicability in gene function, protein evolution, lineage tracing, disease modeling, and gene therapy.

Conclusions:

• Base editors represent a significant advancement in gene-editing technology.
• Optimized base editors hold immense potential for various biomedical and therapeutic applications.
• Further research is needed to address challenges for clinical translation of base editor therapies.