Highly Efficient SiRNA Delivery Mediated by Cationic Helical Polypeptides and Polypeptide-Based Nanosystems

Area of Science:

• Biochemistry
• Molecular Biology
• Nanotechnology

Background:

• RNA interference (RNAi) is a powerful gene regulation mechanism.
• Effective delivery of small interfering RNA (siRNA) into target cells remains a significant challenge for therapeutic applications.

Purpose of the Study:

• To develop and evaluate novel cationic helical polypeptides and polypeptide-based nanosystems for enhanced siRNA delivery.
• To demonstrate the efficacy of these systems for in vitro and in vivo gene silencing, particularly through oral administration.

Main Methods:

• Synthesis and characterization of cationic helical polypeptides and polypeptide-based nanosystems.
• In vitro assessment of siRNA complexation, cellular uptake, and gene silencing efficiency.
• In vivo evaluation of siRNA delivery and therapeutic effects following oral administration in relevant models.

Main Results:

• Cationic helical polypeptides and their derived nanosystems effectively complexed siRNA.
• High transfection efficiency and potent gene silencing were observed in vitro.
• Successful in vivo delivery and gene silencing were achieved via oral administration, demonstrating therapeutic potential.

Conclusions:

• Cationic helical polypeptides and polypeptide-based nanosystems represent a promising platform for safe and effective siRNA delivery.
• Oral administration of these nanocarriers offers a viable strategy for systemic RNAi-based therapies.
• This approach addresses a critical barrier, paving the way for broader clinical translation of RNAi technology.