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Updated: Aug 14, 2026
08:23
CIRCLE-Seq for Interrogation of Off-Target Gene Editing
Published on: November 1, 2024
Circular Logic: Engineering Next-Generation Circular RNA Therapeutics for Precision Oncology
Amr Ali Mohamed Abdelgawwad El-Sehrawy1, Hamzeh J Al-Ameer2, Jasur Rizaev3
1Internal medicine, Diabetes, Endocrinology and Metabolism, Mansoura University, Mansoura, Egypt.
Biotechnology and Bioengineering
|August 13, 2026
Summary
Circular RNA (circRNA) offers enhanced stability and sustained protein expression for precision oncology therapeutics. Advances in translation, delivery, and manufacturing are paving the way for circRNA
Area of Science:
- RNA therapeutics
- Precision oncology
- Biomarkers
Background:
- Circular RNA (circRNA) offers superior stability over linear mRNA due to its lack of free ends.
- Endogenous circRNAs show cancer-specific expression and persistence in biofluids, indicating roles in tumor biology and as biomarkers.
- Circular topology is an active pharmacologic variable, not just a stability feature.
Purpose of the Study:
- Review recent advances in circRNA therapeutics for precision oncology.
- Highlight innovations in circRNA design, delivery, and manufacturing.
- Discuss applications and future directions for circRNA in cancer treatment and diagnosis.
Main Methods:
- Dissection of cap-independent translation initiation (IRES, m6A-driven).
- Exploration of rolling-circle translation for vaccine design.
- Analysis of programmable stability circuits responding to tumor microenvironment cues (miRNA signatures).
- Review of delivery innovations (antibody-guided LNP, EVs, local depots, organ-selective routes).
- Evaluation of safety considerations (immunogenicity, neoantigens).
- Assessment of manufacturing advances (circularization, purification, dsRNA depletion, lyophilization).
Main Results:
- circRNA enables sustained protein expression for days to weeks.
- Delivery systems are becoming more selective and targeted.
- Safety profiles are complex, offering both therapeutic benefits and risks.
- Manufacturing bottlenecks are being addressed, but scalability needs further characterization.
- Key applications include cancer vaccines, cell therapy engineering, tumor suppressor replacement, and bispecific engagers.
Conclusions:
- circRNA topology is a critical, active component of therapeutic design.
- Significant progress has been made in circRNA design, delivery, and manufacturing.
- Further development is needed in pharmacokinetic tracking, scalable manufacturing, validated biomarkers, and regulatory pathways to advance circRNA therapeutics from bench to bedside.
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