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A Nonviral Approach to Generate Transient Chimeric Antigen Receptor T Cells Using mRNA for Cancer Immunotherapy
Published on: February 21, 2025
An overview of current delivery systems in cancer gene therapy
1School of Pharmacy, Memorial University of Newfoundland, 300 Prince Philip Dr, St. John's, NL, Canada A1B 3V6. anas@pharm.mun.ca
Abstract:
The main objective in gene therapy is the development of efficient, non-toxic gene carriers that can encapsulate and deliver foreign genetic materials into specific cell types such as cancerous cells. During the past two decades, enormous research in the area of gene delivery has been conducted worldwide, in particular for cancer gene therapy application. Viral vectors are biological systems derived from naturally evolved viruses capable of transferring their genetic materials into the host cells. Many viruses including retrovirus, adenovirus, herpes simplex virus (HSV), adeno-associated virus (AAV) and pox virus have been modified to eliminate their toxicity and maintain their high gene transfer capability. The limitations associated with viral vectors, however, in terms of their safety, particularly immunogenicity, and in terms of their limited capacity of transgenic materials, have encouraged researchers to increasingly focus on non-viral vectors as an alternative to viral vectors. Non-viral vectors are generally cationic in nature. They include cationic polymers such as poly(ethylenimine) (PEI) and poly(L-lysine) (PLL), cationic peptides and cationic liposomes. The newly described liposomal preparation LPD (liposomes/protamine/DNA), for example, has shown superiority over conventional liposomes/DNA complexes (lipoplexes). Although non-viral vectors are less efficient than viral ones, they have the advantages of safety, simplicity of preparation and high gene encapsulation capability. This article reviews the most recent studies highlighting the advantages and the limitations of various types of gene delivery systems used in cancer gene therapy.
Insights
Developing effective and safe gene delivery systems is crucial for cancer gene therapy. Researchers are exploring both viral vectors and non-viral alternatives like cationic polymers and liposomes, each with unique advantages and limitations.
Area of Science:
- Biomedical Engineering
- Molecular Biology
- Oncology
Background:
- Gene therapy aims to develop efficient, non-toxic carriers for delivering genetic material into target cells, particularly cancer cells.
- Viral vectors, modified from viruses like adenovirus and AAV, offer high gene transfer but face safety and capacity limitations.
- Non-viral vectors, including cationic polymers (PEI, PLL) and liposomes, are being explored as safer alternatives with high gene encapsulation.
Purpose of the Study:
- To review recent advancements in gene delivery systems for cancer gene therapy.
- To highlight the advantages and limitations of various viral and non-viral gene delivery methods.
- To inform the development of improved gene carriers for therapeutic applications.
Main Methods:
- Review of current scientific literature on gene delivery systems for cancer therapy.
- Comparative analysis of viral vectors (retrovirus, adenovirus, HSV, AAV, pox virus) and non-viral vectors (cationic polymers, peptides, liposomes).
- Evaluation of safety, efficiency, immunogenicity, and gene encapsulation capacity of different vectors.
Main Results:
- Viral vectors demonstrate high gene transfer efficiency but raise safety concerns (immunogenicity) and have limited genetic material capacity.
- Non-viral vectors, such as liposomal preparations (LPD), offer improved safety, simpler preparation, and higher gene encapsulation.
- While less efficient than viral vectors, non-viral vectors present a promising alternative for cancer gene therapy.
Conclusions:
- Non-viral vectors are emerging as a safer and more practical option for cancer gene therapy, despite current efficiency challenges.
- Continued research into non-viral vector optimization is essential for overcoming limitations and enhancing therapeutic outcomes.
- The choice of gene delivery system depends on balancing efficiency, safety, and cargo capacity for specific cancer gene therapy applications.
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