Advances in base editing: A focus on base transversions.

Area of Science:

• Genetics
• Molecular Biology
• Biotechnology

Background:

• Single nucleotide variants (SNVs) are the most common cause of human genetic diseases.
• CRISPR-based base editors (BEs) offer direct correction of SNVs, with cytosine base editors (CBEs) and adenine base editors (ABEs) addressing transition mutations.
• Transversion mutations, however, require base replacement and were not correctable by early BEs.

Purpose of the Study:

• To review the basics and recent advances in base transversion editors.
• To highlight the limitations of current base transversion editors.
• To discuss the therapeutic potential of base transversion editors for human diseases.

Main Methods:

• Review of existing literature on base editors, focusing on base transversion editors.
• Analysis of the mechanisms and capabilities of various base transversion editor systems.
• Discussion of the challenges and future directions in the field.

Main Results:

• Cytosine base editors (CBEs) and adenine base editors (ABEs) correct transition mutations (C-to-T, T-to-C, A-to-G, G-to-A).
• Base transversion editors have been developed to correct purine-pyrimidine mutations, complementing existing BEs.
• Base transversion editors are less developed than transition editors but enable correction of all point mutation types.

Conclusions:

• Base transversion editors represent a significant advancement, expanding the scope of CRISPR-based gene correction.
• Further development is needed to overcome limitations and enhance the efficacy of base transversion editors.
• These editors hold considerable promise for treating a wider range of genetic diseases caused by SNVs.