Objective:

To explore the development of circular RNA (circRNA) from a misunderstood entity to a recognized therapeutic modality.

Approach:

• Background: Erik Wiklund, CEO of Circio and co-discoverer of human circRNA, reflects on the initial skepticism surrounding circRNA and its evolution into a promising therapeutic option.
• Discovery: Wiklund and Thomas Birkballe Hansen discovered circRNA while searching for non-coding RNAs regulating genes, leading to the identification of its unique circular structure, which had not been previously described in human cells.
• Research Evolution: Post-discovery, research focused on identifying more circRNAs and their biological functions, revealing their role as microRNA sponges and contributing to the understanding of gene regulation.

Key Findings:

• CircRNA was initially viewed skeptically but gained recognition for its biological functions starting in 2013, particularly after a pivotal paper published by Thomas Birkballe Hansen.
• CircRNA's stability makes it a more durable alternative to mRNA for therapeutic applications, addressing mRNA's instability issues.
• The discovery of circRNA's function as a microRNA sponge opened new avenues for understanding gene regulation and therapeutic potential.

Interpretation:

CircRNA has transitioned from being considered an artifact to a significant player in RNA-based therapies, attracting substantial investment and research interest.

Limitations:

• Initial skepticism and complexity in the biological functions of circRNA may hinder wider acceptance among researchers and clinicians.
• The early research faced challenges in publication due to the novelty and complexity of findings, which made it difficult for reviewers to accept.

Conclusion:

The rise of circRNA represents a significant advancement in RNA research, highlighting its potential for future therapeutic developments.