Transductional and transcriptional targeting of cancer cells using genetically engineered viral vectors

Area of Science:

• Biotechnology
• Molecular Biology
• Oncology

Background:

• Adenovirus (Ad) and adeno-associated virus (AAV) gene delivery vectors exhibit poor efficiency and selectivity in cancer treatment.
• This inefficiency stems from low viral receptor expression on cancer cells and high expression on healthy tissues like the liver.

Purpose of the Study:

• To enhance the targeting and transduction capabilities of Ad and AAV vectors in cancer cells.
• To evaluate the efficacy of a SIGYPLP-targeting peptide integrated into viral capsids.
• To assess the activity of the FLT-1 promoter in transduced cancer cells for dual targeting.

Main Methods:

• Adenovirus (Ad) and adeno-associated virus (AAV) vectors were modified by inserting the SIGYPLP-targeting peptide into their capsids.
• Transduction efficiency was tested across a panel of twelve cancer cell lines.
• The activity of the FLT-1 gene therapy promoter was evaluated in successfully transduced cell lines.

Main Results:

• Six out of twelve tested cancer cell lines (C8161, PC-3, G-CCM, MKN-45, LnCAP, and A549) demonstrated successful transduction.
• Transduction occurred independently of the cells' native viral tropism.
• The FLT-1 promoter was active in three of the six successfully transduced cell lines.

Conclusions:

• Engineering Ad and AAV vectors with the SIGYPLP-targeting peptide significantly improves their ability to transduce cancer cells.
• This modified vector system demonstrates potential for selective gene delivery to cancer cells, overcoming limitations of native viral tropism.
• The combined use of the targeting peptide and the FLT-1 promoter offers a promising strategy for dual targeting in cancer gene therapy.