Tumor-selective targeted delivery of genes and antisense oligodeoxyribonucleotides via the folate receptor

Area of Science:

• Oncology
• Gene Therapy
• Molecular Targeting

Background:

• Gene therapy holds significant promise for cancer treatment, but clinical application is hindered by the lack of safe, effective, and tumor-selective gene transfer vectors.
• Targeted gene delivery via cellular receptors is an emerging strategy to improve the efficacy and tumor selectivity of gene therapy.

Purpose of the Study:

• To evaluate the potential of folate receptor (FR)-targeted vectors for enhancing tumor-selective gene delivery in cancer therapy.
• To explore the efficacy and safety of various FR-targeted vectors, including viral and nonviral systems, for delivering therapeutic genes and oligodeoxyribonucleotides (ODNs).

Main Methods:

• Development and evaluation of FR-targeted vectors, such as folate-derivatized adenoviruses, cationic polymers, and liposomes (including pH-sensitive variants).
• Assessment of vector selectivity using cell culture assays targeting FR-expressing cancer cells.
• In vivo testing of FR-targeted vectors in preclinical cancer models to evaluate tumor-specific gene transfer activity.

Main Results:

• FR-targeted vectors consistently demonstrated high FR-selectivity in vitro cell culture assays.
• These vectors showed promising tumor-specific gene transfer activity in various in vivo preclinical models.
• FR-targeted vectors offer theoretical advantages over non-targeted vectors for in vivo cancer gene therapy.

Conclusions:

• Folate receptor-targeted vectors represent a viable and promising approach for achieving tumor-selective gene delivery in cancer therapy.
• Further preclinical investigation is warranted to fully ascertain the therapeutic potential of these FR-targeted vectors for clinical application in cancer gene therapy.