Delivering the Goods for Genome Engineering and Editing.

Area of Science:

• Genetics and Molecular Biology
• Virology
• Biotechnology

Background:

• Genome evolution and microbial life are foundational to genetic therapies.
• Genetic engineering tools include transposases, recombinases, and nucleases derived from natural proteins.
• Conventional gene therapies aim for sustained gene expression, unlike transient genomic tools.

Purpose of the Study:

• To review current intracellular protein production strategies for gene therapy delivery.
• To explore emerging direct protein delivery methods, including recombinant protein transfer and lentiviral transduction.
• To discuss the potential of engineered lentiviral particles for efficient gene editing.

Main Methods:

• Analysis of current gene therapy delivery strategies (DNA, RNA, viral templates).
• Evaluation of advantages and challenges of intracellular protein production.
• Description of direct protein delivery approaches and engineered lentiviral systems.

Main Results:

• Intracellular protein production via DNA, RNA, or viral vectors presents specific challenges.
• Direct protein delivery offers a promising alternative for transient genomic modifications.
• Engineered "all-in-one" lentiviral particles can co-deliver effector proteins and donor sequences.

Conclusions:

• Optimized delivery of DNA, RNA, or proteins is crucial for advancing gene therapy.
• Direct protein delivery and novel viral vector engineering are key to efficient somatic gene therapies.
• The development of transient, targeted genomic tools is essential for therapeutic success.