Circular RNAs (circRNAs) represent a unique class of RNA molecules with closed-loop structures that lack 5′ or 3′ ends, conferring them with high stability and resistance to degradation. While natural circRNAs can function as non-coding RNAs or encode proteins, their physiological roles have been increasingly recognized, including acting as miRNA sponges, regulating protein expression, and modulating cellular activities. Recent advancements have shed light on the biogenesis of circRNAs, ranging from back splicing to canonical linear splicing, driven by spliceosomes andcis-regulatory elements. The discovery of synthetic circRNAs has opened new avenues for their use as therapeutic agents, vaccines, and biosensors, presenting exciting opportunities in disease management and diagnostics.
The design and synthesis of synthetic circRNAs are crucial considerations in leveraging these molecules for biomedical applications. Strategies to enhance circRNA circularization and translation efficiency include the use of intronic complementary sequences, ribozymes, and permuted intron-exon systems. Chemical and enzymatic approaches are employed for circRNA synthesis, with a focus on enhancing stability and translation efficiency while mitigating immunogenicity. The translation potential of circRNAs has been demonstrated through the identification of internal ribosome entry sites (IRES) and N6-methyladenosine (m6A) RNA modifications that enable cap-independent translation. The immunogenicity of circRNAs must be carefully evaluated and managed for optimal therapeutic outcomes, with purification methods and modifications playing crucial roles in modulating immune responses.
Endogenous circRNAs have emerged as promising therapeutic targets for various diseases, including cancer, cardiovascular disorders, and neurological conditions. Dysregulation of circRNA expression has been implicated in disease pathogenesis, presenting opportunities for targeted interventions such as RNA interference (RNAi) to modulate circRNA levels and mitigate disease progression. In cancer, circRNAs have been identified as key regulators of tumor growth, angiogenesis, and metastasis, making them attractive targets for therapeutic intervention. In cardiovascular diseases and neurodegenerative disorders, circRNAs have shown modulatory roles in cellular processes, offering potential avenues for therapeutic development to promote tissue repair and regeneration post-injury.
The development of circRNA-based therapeutics and vaccines requires a deep understanding of their biogenesis, physiological functions, and design considerations. By leveraging the unique properties of circRNAs, such as their stable closed-loop structures and diverse functions as miRNA sponges, protein regulators, and modulators of cellular activities, researchers can harness the therapeutic potential of these molecules for precision medicine and disease management. The strategic synthesis and design of synthetic circRNAs, coupled with targeted approaches to modulate endogenous circRNA expression, hold promise for the future of RNA-based therapeutics and vaccine design, paving the way for innovative treatments in a wide range of diseases and disorders.
- Understanding the biogenesis and physiological functions of circRNAs is essential for designing effective therapeutic strategies.
- Strategic synthesis and design of synthetic circRNAs play a crucial role in enhancing stability, translation efficiency, and immunogenicity management.
- Targeting dysregulated endogenous circRNAs holds promise for therapeutic interventions in cancer, cardiovascular diseases, and neurological disorders.
- The diverse functions of circRNAs, from miRNA sponges to protein regulators, offer versatile opportunities for therapeutic development and precision medicine.
Tags: drug delivery, lipid nanoparticles, upstream, formulation, downstream, theranostics, fungi, biosensors, yeast
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