Internal ribosome entry site-based vectors for combined gene therapy

Area of Science:

• Molecular Biology
• Genetics
• Biotechnology

Background:

• Gene therapy offers potential for incurable diseases, with combined approaches showing enhanced efficacy.
• Internal ribosome entry sites (IRESs) are RNA elements facilitating cap-independent translation initiation.
• IRES elements enable the co-expression of multiple genes from a single messenger RNA (mRNA) transcript.

Purpose of the Study:

• To highlight the utility of Internal ribosome entry sites (IRESs) in developing multi-gene therapies.
• To explore the application of IRES-mediated translation in advanced gene transfer strategies.
• To review the therapeutic potential of IRES-based vectors in treating complex diseases.

Main Methods:

• Design of multi-cistronic vectors utilizing IRES elements for simultaneous gene expression.
• Application of IRES-driven gene transfer in viral and non-viral vector systems.
• Evaluation of IRES functionality in specific cellular contexts and disease models.

Main Results:

• IRES elements successfully enabled the co-expression of multiple therapeutic genes from a single mRNA.
• IRES-based vectors demonstrated tissue specificity and function under cellular stress conditions, including hypoxia.
• Successful preclinical and clinical applications of IRES-mediated gene therapy showed therapeutic benefits.

Conclusions:

• Internal ribosome entry sites (IRESs) are valuable tools for combined gene therapy, enabling efficient multi-gene expression.
• The unique properties of IRESs, including stress-induced translation, make them suitable for treating ischemic diseases and cancers.
• IRES-based gene therapy holds significant promise for a range of pathologies, including cardiovascular and degenerative diseases.