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Gene Delivery

Gene Delivery

Gene therapy is the treatment of diseases by targeting genomic DNA, mRNA, siRNA and microRNA to modulate gene expression to correct or compensate for the disease caused by defective and abnormal genes. The significance of gene therapy is that it involves manipulating genes within human cells to treat or control disease, can promote reproduction, eliminate disease, and has flexibility in the innovation process.

Approaches to Achieve Gene Therapy

With the rapid development of gene therapy, its potential applications have expanded to acquired diseases such as cancer, and many nucleic acid analogs have been developed to target coding or non-coding sequences of the human genome for gene regulation. Gene therapy can be achieved through the delivery of DNA, mRNA and siRNA.

Principle of gene therapy.Principle of gene therapy. (Ibraheem D, et al., 2013)

  • DNA Delivery
    In recent years, the introduction of DNA into target cells can achieve gene therapy for the treatment of many serious incurable diseases such as cancer and genetic diseases.
  • siRNA Delivery
    After delivery of siRNA to target cells, target genes can be reversibly silenced to achieve gene therapy.
  • mRNA Delivery
    As a new class of nucleic acid drugs, mRNA can be used in gene therapy, vaccine, gene editing and other fields after delivery to target cells.

Delivery System for Gene Therapy

The application of gene therapy is limited due to the difficulty of delivering nucleic acid analogs to target cells, target organs or target tissues, so it is necessary to develop an ideal delivery system. The ideal system for gene therapy should not elicit a strong immune response, be able to transport nucleic acids of any size, be able to deliver genes to target cells, and be easy to prepare.

  • Lipids
    Liposomes, which have long been used to deliver genes, are spherical delivery systems with hydrophilic polar head groups and hydrophobic tails. The head group of liposomes can combine with the anionic phosphate group of nucleic acid to form a lipid complex through electrostatic interaction to realize gene therapy. Lipids are biodegradable and less toxic than other delivery systems.

Structure of lipid nanoparticles (LNPs) comprising of all the components.Structure of lipid nanoparticles (LNPs) comprising of all the components. (Wahane A, et al., 2020)

  • Cationic Polymers
    Compared with other delivery systems, delivery materials containing cationic polymers tend to aggregate and package negatively charged nucleic acids, resulting in higher transfection efficiency. As a new class of cationic polymer materials, (amino co-ester) (PACE)-based polymers are able to reduce cytotoxicity by reducing cationic charge and possess cleavable ester moieties that hydrolyze under biological conditions.

Chemical structures of commonly used cationic polymers for nucleic acid delivery.Chemical structures of commonly used cationic polymers for nucleic acid delivery. (Wahane A, et al., 2020)

VLP as Delivery System for Gene Therapy

Virus-like particles (VLPs) are considered natural nanomaterials due to their size range of 20 to 500 nm. VLPs can accommodate genes, avoid their enzymatic degradation in body fluids, and deliver them to the target site for gene therapy, similar to drug delivery.

VLPs can be produced by various platforms (bacteria, yeast, plants, etc.), and then gene-loaded into protein capsids by gene fusion or chemical conjugation, and then coupled with nanoparticles, polymers or biomolecules to increase Cytocompatibility and binding efficiency to host cell receptors. After the virus-like nanoparticle with the target gene binds to the host cell receptor, the conjugated molecule is degraded, allowing the virus-like nanoparticle to bypass the cell membrane and enter the cell. The capsid proteins of VLPs are either degraded by cytoplasmic enzymes or bind to the nucleus to release therapeutic genes.

Mechanisms of VLP delivery in gene therapy.Mechanisms of VLP delivery in gene therapy. (Jeevanandam J, et al., 2019)

How We can Help

As a global leader in the production and application of VLPs from VLPlantTM platform, CD BioSciences leverages its expertise to help our clients develop gene therapies. We are good at tailoring our services to the needs of our clients. Please contact us if you are interested.

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  1. Ibraheem D.; et al., Gene therapy and DNA delivery systems. Int J Pharm. 2013, 459: 70-83.
  2. Wahane A.; et al., Role of Lipid-Based and Polymer-Based Non-Viral Vectors in Nucleic Acid Delivery for Next-Generation Gene Therapy. Molecules. 2020, 12:1-23.
  3. Jeevanandam J.; et al., Virus-like nanoparticles as a novel delivery tool in gene therapy. Biochimie. 2019, 157:38-47.
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