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Viral and Non-Viral Delivery Systems: Gateways to Effective Gene Therapy in Cancer Treatment

Viral Delivery Systems: Nature’s Efficient Vectors

Adeno-Associated Viruses (AAVs)

AAVs are among the most widely used vectors in gene therapy due to their:

  • Low immunogenicity (mild immune response)
  • Ability to infect dividing and non-dividing cells
  • Stable and long-term expression of genes

Lentiviruses

Lentiviral vectors, derived from HIV, can integrate into the host genome, allowing for stable gene expression. They are particularly useful for:

  • Engineering T cells in CAR-T therapies
  • Ex vivo gene editing of hematopoietic stem cells



Oncolytic Viruses

These are genetically modified viruses that selectively infect and kill cancer cells while delivering therapeutic genes. They also stimulate an anti-tumor immune response, making them dual-function agents.

Examples include:

  • Talimogene laherparepvec (T-VEC) for melanoma
  • Engineered adenoviruses for solid tumors

Non-Viral Delivery Systems: Safer and More Customizable

1

Lipid Nanoparticles (LNPs)

LNPs have gained prominence following their success in mRNA COVID-19 vaccines. In cancer therapy, LNPs are used to deliver:

  • mRNA encoding tumor antigens or immune-modulating proteins
  • CRISPR components for gene editing
  • siRNA for gene silencing

2

Polymeric Nanoparticles

These synthetic polymers can encapsulate DNA, RNA, or proteins. Advantages include:

  • Tunable size and surface properties
  • Controlled release profiles
  • Co-delivery of multiple agents (e.g., gene therapy + chemotherapy)


3

Exosomes and Cell-Derived Vesicles

Exosomes are natural nanocarriers secreted by cells. As delivery systems, they offer:

  • Biocompatibility and low immunogenicity
  • Intrinsic targeting properties based on surface markers
  • Ability to cross biological barriers, such as the blood-brain barrier

These vesicles are promising for delivering RNA-based therapies and are under investigation for glioblastoma, pancreatic, and breast cancers.


Emerging Hybrid Systems: Combining the Best of Both Worlds

To overcome the limitations of individual platforms, researchers are developing hybrid delivery systems, such as:

Virus-like particles (VLPs): Non-infectious particles mimicking viruses without viral genomes
Lipid-coated viral particles: Enhanced with tumor-targeting ligands
DNA origami: Self-assembling nanostructures capable of precise delivery and responsive release


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