Abstract

AbstractOver the last 30 years, genetically engineered DNA has been tested as novel vaccination strategy against various diseases, including human immunodeficiency virus (HIV), hepatitis B, several parasites, and cancers. However, the clinical breakthrough of the technique is confined by the low transfection efficacy and immunogenicity of the employed vaccines. Therefore, carrier materials were designed to prevent the rapid degradation and systemic clearance of DNA in the body. In this context, biopolymers are a particularly promising DNA vaccine carrier platform due to their beneficial biochemical and physical characteristics, including biocompatibility, stability, and low toxicity. This article reviews the applications, fabrication, and modification of biopolymers as carrier medium for genetic vaccines.

Highlights

  • DNA vaccines are bacterial plasmids designed to carry a specific encoding gene, which is responsible for expression of the desired antigen in the host and leads to the induction of an immune response.[7,8]

  • Puneet is co-inventor of several U.S and international patents and has published extensively in the field of drug delivery. He is a member of various professional organisations including the American Association of Pharmaceutical Scientists (AAPS), where he is serving as a steering committee member of the AAPS Nanotechnology Community since August 2015

  • This strategy was employed to facilitate unpacking of pDNA from polymer carriers such as dextran,[147,162] Hyaluronic Acid (HA),[68] polyarginine[89] and LLO,[78,79] which were modified with positively charged groups via disulphide bonds

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Summary

DNA vaccines

The development of vaccines has been one of the most significant advances of modern medicine and has led to improved public health and life expectancy. There are many ongoing human clinical trials that target various types of cancer, autoimmune diseases and infectious diseases, such as human papilloma virus (HPV), HIV, hepatitis B and coronavirus (Table 1).[5,15] Results of these first clinical trials reported DNA vaccines to be safe and well tolerated, but showed low immunogenicity, which was attributed to insufficient protein expression levels.[5,11]. This low efficacy can be overcome by optimisation of the plasmidencoded antigen to increase antigen expression per cell or by increasing the transfection rate through polymer and lipid formulations, as well as enhancement of the immune response by addition of molecular adjuvants.[9]. NCT number (for identification) NCT04336410 NCT04445389 NCT04463472 NCT02776761 NCT03606213 NCT03603808 NCT04090528 NCT03600350 NCT03532217 NCT03199040 NCT04251117 NCT03750071 NCT02204098 NCT00788164 NCT03655756

DNA vaccines: mode of action
Delivery of DNA vaccines
Biopolymers as DNA vaccine carriers
Strategies for improved DNA condensation
Improved stability and solubility of DNA biopolymer systems
Improved cell uptake
Non-specific cell uptake
Target-specific cell uptake
Designing Carriers that Enable Endosomal Escape
Improved pDNA release and delivery to the nucleus
DNA Vaccine Delivery Materials with Immunostimulatory effects
Findings
Conclusion and future directions
Full Text
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