DNA vaccines and DNA hydrogels.
Continuous innovations propel the biomedical field in a significant manner. Deoxyribonucleic acid (DNA) vaccines are third generation vaccines that incorporate a DNA sequence encoding for antigenic proteins from a pathogen. After administration of the plasmid DNA vaccine, the DNA undergoes transcription then translation to form the antigenic proteins, which elicit both an innate and humoral immune response that confers immunological protection against the disease. On the other hand, DNA hydrogels as polymeric materials are hydrogels that comprise of three-dimensional networks of DNA polymeric chains. The specificity and ability to combine with other functional materials confers DNA hydrogel, an array of possible applications. The history of the technologies shows substantial development over the years. The impact of DNA vaccines and DNA hydrogels in the biomedical field is indisputable.
DNA vaccine technology pioneered in the 1990s with retroviral vectors in chicken prompted by the use of the attenuated virus as an expression vector for vaccination in 1982. The technique, however, was met with a lot of skepticism. The first studies for DNA vaccines targeted avian diseases, particularly the gene for the hemagglutinin of bird flu using a replication-competent avian retroviral vector (Fynan, 968). Transfection resulted in the expression of the influenza hemagglutinin protein, which conferred protection against the influenza virus, with the control group succumbing to the virus. Several other studies proved the capacity of DNA vaccines in achieving 100% protection over diseases. In 1992 the technology received public acceptance in the Cold Spring Harbor Vaccine Meeting. The technology advanced from the use of retroviral vectors to non-retroviral DNA vectors, which entailed using a mammalian expression plasmid—five years after the first demonstration, DNA vaccines reached the clinics (Liu,68). However, twenty-five years after the inception of the technology, there is no single licensed DNA vaccine for humans.
The use of hydrogels dates back to the 1960s with their biomedical applications stemming up from the 1970s. The first generation of hydrogels contained crosslinks with chemical alterations of the monomer or polymer with an initiator resulting in materials with high swelling and adequately excellent mechanical properties. The second generation that developed in the 1970s contained the ability to respond to stimuli like temperature, pH, or concentration of solutions, presenting a plethora of possible applications in the biomedical field (Chirani, 2). The third generation hydrogels focused on the development of complex materials. DNA hydrogels resulted from the third generation of hydrogels and involved molecular interaction-based sensing of analytes. In 1996 two researchers utilized DNA as linkers in the preparation of swelling hydrogels. Early approaches used DNA building blocks mixed in solutions that, in turn, formed three-dimensional structures as a result of complementary interactions of DNA strands on separate building blocks. After that, DNA incorporation in hydrogels presented a plethora of applications.
The impact of DNA technologies is overly significant via multiple applications. DNA vaccines are advantageous because they stimulate both cellular and humoral immune responses. The production of antibodies from B lymphocytes is the most effective defenses that produce a vaccine’s long-lasting effects as the antibodies produced develop into memory antibodies, thus providing a lasting impact of the vaccine. The efficacy and safety contribute to the effect of DNA vaccines in protecting against veterinary diseases like the Nile virus in horses and canine melanoma. DNA hydrogels are significant in impacting immunotherapy, drug delivery, biosensing, and tissue engineering. They have revolutionized the detection of in vivo and in vitro analytes that are important for diagnosis and personalized healthcare approaches.
There are currently no licensed human DNA vaccines used in clinical settings. However, human trials are underway for the development of DNA vaccines for malaria, Ebola, influenza, and Acquired immunodeficiency syndrome (AIDS), and herpes virus (Khan, 26). From the human trials in efforts to develop human DNA vaccines, the technology shows very poor immunogenicity. Some of the factors contributing to the reduced immunogenicity include extracellular DNA degradation, and tolerance induction as a result of delivery. The recent human trials on the development of an HIV DNA vaccine showed no antibody response elicited by the vaccine with a mild localized reactivity at the injection site (Hobernik, 4). There is a need to enhance and optimize the following steps after transfection with the plasmid DNA vaccine to ensure efficiency in the development of humoral and cell-induced immune response.
The present state of DNA hydrogels largely embeds in its applications in the biomedical field. The applications include biosensing, drug delivery, and immunomodulation. Biosensing techniques entail using a functional DNA cross-linker as a sensor for the detection of specific molecules like ions or compounds. For instance, the recognition of thrombin which is significant in indicating kidney inflammation that is present in certain cancers, diabetes, and autoimmune diseases (Gačanin, 3). In drug delivery for anticancer drugs, DNA hydrogels confer high efficacy and reduce off-targets side effects. Lastly, as immunomodulators, DNA hydrogels use unmethylated cytosine phosphate guanine dinucleotide motifs to stimulate the immune system and ensure sustained signaling.
The development of DNA technologies like DNA vaccines and DNA hydrogels proves essential in advancing biomedical solutions. The inception of these technologies faced criticism and skepticism, but over the years have garnered acceptance and influenced multiple approaches of healthcare. With a plethora of promising applications, the need to optimize DNA technologies such as DNA vaccines for human diseases is paramount in maximizing solutions for the biomedical field. Additionally, exploring new forms of DNA hydrogels will advance the filed further.
References
Chirani, Naziha, et al. “History and applications of hydrogels.” Journal of biomedical sciences 4.2 (2015). doi:10.4172/2254-609X.100013
Fynan, Ellen F., Shan Lu, and Harriet L. Robinson. “One Group’s Historical Reflections on DNA Vaccine Development.” Human gene therapy 29.9 (2018): 966-970. doi: 10.1089/hum.2018.066
Gačanin, Jasmina, Christopher V. Synatschke, and Tanja Weil. “Biomedical Applications of DNA‐Based Hydrogels.” Advanced Functional Materials 30.4 (2020): 1906253. https://doi.org/10.1002/adfm.201906253
Hobernik, Dominika, and Matthias Bros. “DNA vaccines—how far from clinical use?.” International journal of molecular sciences 19.11 (2018): 3605. doi: 10.3390/ijms19113605
Khan, Kishwar Hayat. “DNA vaccines: roles against diseases.” Germs 3.1 (2013): 26. doi: 10.11599/germs.2013.1034
Liu, Margaret A. “DNA vaccines: an historical perspective and view to the future.” Immunological reviews 239.1 (2011): 62-84. doi: 10.1111/j.1600-065X.2010.00980.x
