In vivo selection of tumor-targeting RNA motifs

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Targeting cancer metastases in vivo remains a significant challenge in oncology.
• RNA oligonucleotides offer potential as targeted therapeutic agents due to their specificity.
• Hepatic metastases from colorectal cancer are a common and difficult-to-treat clinical problem.

Purpose of the Study:

• To identify nuclease-resistant RNA oligonucleotides capable of localizing to hepatic colon cancer metastases in vivo.
• To characterize selected RNA molecules for their potential as targeted therapeutic agents.

Main Methods:

• Screening of a large library of nuclease-resistant RNA oligonucleotides in tumor-bearing mouse models.
• In vivo selection and identification of RNA molecules with tumor-homing capabilities.
• Characterization of a lead RNA aptamer for its binding target.

Main Results:

• Identification of several RNA oligonucleotides that demonstrated localization to hepatic colon cancer metastases.
• One selected molecule is an RNA aptamer that specifically binds to the p68 RNA helicase.
• p68 RNA helicase is known to be upregulated in colorectal cancer tissues.

Conclusions:

• Nuclease-resistant RNA oligonucleotides can be effectively selected for in vivo targeting of specific cancer metastases.
• The identified RNA aptamer targeting p68 represents a promising candidate for further development in colorectal cancer therapy.
• This approach provides a novel strategy for developing targeted therapies against liver metastases.