Efforts to Downsize Base Editors for Clinical Applications

Area of Science:

• Biotechnology
• Molecular Biology
• Genetics

Background:

• Clustered regularly interspaced short palindromic repeats (CRISPR) technology has revolutionized gene editing.
• Base editors (BEs) provide precise single-nucleotide editing without inducing DNA double-strand breaks (DSBs).
• The large size of BEs hinders efficient delivery, especially via adeno-associated virus (AAV) vectors, limiting clinical applications.

Purpose of the Study:

• To emphasize the significance of reducing base editor (BE) size for therapeutic gene editing.
• To review recent advancements in strategies for downsizing BEs.
• To discuss ongoing efforts to address other BE limitations for improved in vivo gene editing.

Main Methods:

• Reviewing literature on CRISPR-based gene editing tools, specifically base editors.
• Analyzing strategies for BE size reduction, including domain truncation and component replacement.
• Examining methods to overcome delivery and other challenges associated with BEs.

Main Results:

• Various size-reduction strategies for BEs have been developed.
• These strategies aim to maintain editing efficiency while improving deliverability.
• Progress is being made in addressing other limitations for enhanced in vivo gene editing.

Conclusions:

• Downsizing base editors (BEs) is essential for their successful clinical translation and efficient AAV-mediated delivery.
• Ongoing research focuses on optimizing BEs for therapeutic applications by addressing size and delivery challenges.
• These advancements hold promise for improving the efficacy and safety of in vivo gene editing therapies.