Multifunctional aptamer-miRNA conjugates for targeted cancer therapy

Area of Science:

• Biotechnology
• Molecular Biology
• Oncology

Background:

• MicroRNAs (miRNAs) are crucial regulators of cellular pathways involved in disease.
• Effective and safe delivery of therapeutic miRNAs to target tissues remains a significant challenge for clinical applications.
• The receptor tyrosine kinase Axl is an oncogenic target implicated in tumor progression.

Purpose of the Study:

• To develop and evaluate aptamer-miRNA conjugates for targeted delivery of tumor suppressor let-7g miRNA.
• To investigate the potential of these conjugates to inhibit the growth of Axl-expressing tumors.

Main Methods:

• Conjugation of let-7g miRNA to an Axl-targeting aptamer (GL21.T).
• Demonstration of selective delivery to Axl-expressing cells.
• Assessment of miRNA processing and target gene silencing.
• Evaluation of tumor growth inhibition in a lung adenocarcinoma xenograft model.

Main Results:

• Successful development of aptamer-miRNA conjugates.
• Selective cellular uptake and RNA interference-mediated gene silencing by the conjugate.
• Significant reduction in tumor growth in vivo.
• Demonstrated therapeutic potential of aptamer-guided miRNA delivery.

Conclusions:

• Aptamer-miRNA conjugates represent a novel and effective platform for targeted miRNA delivery.
• This approach offers a promising strategy for developing miRNA-based cancer therapeutics.
• The developed conjugates can inhibit tumor growth by delivering tumor suppressor miRNAs to target cells.