Group I Intron-Based Therapeutics Through Trans-Splicing Reaction.

Area of Science:

• Biochemistry
• Molecular Biology
• RNA Catalysis

Background:

• The discovery of catalytic RNA (ribozymes) in 1982 revolutionized understanding of RNA's biological roles beyond genetic information carriers.
• Ribozymes possess unique three-dimensional structures enabling catalytic activity, expanding their known functions in biological processes.

Purpose of the Study:

• To explore the potential of engineered ribozymes, particularly group I intron-based trans-splicing ribozymes, as therapeutic agents.
• To review the current status and future prospects of trans-splicing ribozyme therapeutics.

Main Methods:

• Classification of naturally occurring ribozymes into self-cleavage and self-splicing categories.
• Engineering of self-acting ribozymes into trans-acting ribozymes through identification of catalytic centers and base-pairing recognition.
• Focus on Tetrahymena group I intron-based ribozymes for therapeutic applications.

Main Results:

• Ribozymes can be engineered from self-acting to trans-acting forms, enhancing their utility in gene therapy.
• Group I intron-based trans-splicing ribozymes can simultaneously degrade and repair target RNAs, creating therapeutic molecules.
• Successful applications of trans-splicing ribozymes in gene therapy and molecular imaging for various diseases have been demonstrated.

Conclusions:

• Trans-splicing ribozymes, especially those derived from Tetrahymena group I introns, represent a powerful tool for gene therapy.
• These ribozymes maintain endogenous gene regulation while correcting target RNAs, offering a unique therapeutic advantage.
• Continued advancements in trans-splicing ribozyme technology hold significant promise for treating diverse pathogenic conditions.