Microneedles vs. Other Transdermal Technologies
Boris Stoeber, Raja K Sivamani, Howard I. Maibach in Microneedling in Clinical Practice, 2020
The original biolistic particle delivery system, or gene gun, was designed for delivering exogenous DNA (transgenes) into plant cells. The payload is typically a particle of a heavy metal coated with DNA (typically plasmid DNA). This has been developed into biolistic injectors delivering a “shotgun” burst of nano- or microparticles into the skin (Figure 5.5 right), injectors that have been effective for the immunization of antigens including influenza and malaria, and also in anticancer applications in a range of animals (mice, rat, ferrets, monkeys, etc.) and humans (79–82). Clinical assessment of biolistic particle delivery reports transient localized pain and tissue damage (erythema, irritation, etc.); thus, like liquid biolistic injection, the technique is most suitable to vaccination.
Adeno-Associated Virus-Based Delivery Systems
Kenneth L. Brigham in Gene Therapy for Diseases of the Lung, 2020
Stable gene transduction in skeletal muscle would be desirable both as a treatment of primary muscle disorders and as an in vivo reservoir for soluble circulating proteins such as insulin in diabetes. One group has developed AAV gene transfer to cultured human myoblasts with the goal of later injection into skeletal muscle (163). AAV was the basis of the plasmid pCKM-gfp, a construct using the human CKMmuscle promoter and the green fluorescent protein cDNA as the reporter gene. The cell line was transfected using the gene gun (BioRad) and gold microspheres coated with plasmid DNA. This gene gun accomplished between 1% and 5% transfection efficiency after 4 days in culture. Injection of the naked plasmid DNA directly into murine quadriceps skeletal muscle resulted in much higher efficiency at 4 days, leading the authors to speculate that maximal activity may require differentiated or multinucleated cells. However, it has been observed with other vectors that naked plasmid DNA is very effective in skeletal and cardiac muscle in general (164-172).
Methods for Labeling Nonphagocytic Cells with MR Contrast Agents
Michel M. J. Modo, Jeff W. M. Bulte in Molecular and Cellular MR Imaging, 2007
Mechanical approaches that have been used primarily to introduce DNA or plasmids into the nucleus have been modified to directly introduce MRI contrast agents into cells. The gene gun fires DNA, plasmids, or DNA-coated nanoparticles directly into cells in culture, driving the particles through the cell membrane or directly into the nucleus,96,97 using a ballistic gas charge. SPIO nanoparticles and magnetic beads have been introduced into stem cells using a gene gun with high labeling efficiency,98 and the cells were implanted into rats, but no information was provided about the effects of the method on long-term cell viability, proliferation, differentiation capabilities, or reactive oxygen species. It should be noted that the gene gun approach is indiscriminant and will introduce MRI SPIO nanoparticles directly into the cell nucleus. Although it is beneficial to deliver DNA directly into the nucleus, the presence of SPIO nanoparticles in the nucleus could initiate a Fenton reaction and, through Haber-Weiss chemistry,99 result in the development of free radicals that could cause damage to DNA.
Cancer vaccines as a targeted immunotherapy approach for breast cancer: an update of clinical evidence
Published in Expert Review of Vaccines, 2022
Maryam Abbaspour, Vajihe Akbari
DNA vaccines are bacterial plasmids generated to deliver TA-encoding genes that create or enhance an adaptive immune response to TA-bearing tumor cells [120]. The main strength of DNA vaccines is that they can activate CD4 and CD8 T cells as well as indirectly the humoral immunity by providing antigens encoded by MHC class I and class II [121]. So far, there are no approved DNA vaccines for use in humans and they are undervaluation in phase I or II clinical studies. To enhance efficient immune responses of DNA vaccines, a plasmid delivery system was optimized and they were often developed in combination with other vaccines platforms therapies. The most common methods used to increase transfection efficiencies, such as localized delivery system, electroporation, sonication, and gene gun, can overcome the barriers (intra- or extracellular) to DNA transfer [122,123]. To induce protein synthesis, DNA requires passing through the nuclear membrane. DNA vaccines can integrate into the host genome leading to insertional mutagenesis, chromosomal instability, and oncogenic transformation. The expression of DNA-encoded proteins can be taken place over months to years, depending on vector [124].
GOLD: human exposure and update on toxic risks
Published in Critical Reviews in Toxicology, 2018
Recognising the vast array of its uses and opportunities for human contact, the actual incidence of toxic reactions to metallic gold is very low, probably on account of its chemically unreactive properties. However, since the classical studies of Jacques Forestier and K. Lande in the 1920’s, gold therapies therapies for rheumatoid arthritis have been commonplace (Research Subcommittee of the Empire Rheumatism Council 1960; Davis 1988; Wright 1984). These are toxic drugs and despite the excellent therapeutic record, concern is expressed regarding the high prevalence of potentially serious side effects associated with auranofin, sodium aurothiomalate and aurothioglucose, especially in pregnant women. The mode of action of these drugs in relieving inflammation is not fully understood but in aurothiomalate and aurothioglucose, it is postulated that the thiol moiety is the active and more toxic part of the molecule rather than the metal (Jellum and Munthe, 1980). A range of other therapies have been devised in recent years with the advent of gene targeting, immune modulation and nanotechnology, where gold as nanoparticles, tubules, rods and cages have been engineered with coatings and formulations as in the gene gun technology for anticancer treatment. Although the technologies are devised to achieve apoptotic changes, mutagenicity and death in specific cell types, there is little evidence that metallic gold per se is a ‘toxic factor’, it is merely an inert carrier for the agents that target diseased tissue.
Modern vaccine strategies for emerging zoonotic viruses
Published in Expert Review of Vaccines, 2022
Atif Ahmed, Muhammad Safdar, Samran Sardar, Sahar Yousaf, Fiza Farooq, Ali Raza, Muhammad Shahid, Kausar Malik, Samia Afzal
The major strategies used to produce plant-based vaccines are nuclear, transplastomic, and viral vector transformation. Nuclear transformation is a very simple and widely used method because the foreign antigen is inserted into the nuclear genome. Agrobacterium tumefaciens or gene gun-mediated transformation is used for gene transfer. The nuclear transformation results in the continuous production of recombinant proteins. Additionally, nuclear transformation also results in the post-translational modification that takes place in eukaryotic systems [93,94]. But it is also coupled with some disadvantages including, lower expression level, gene silencing, position effect, and a chance of contamination. The chloroplast transformation overcomes some of the drawbacks of nuclear transformation, which has hampered commercialization as a plant-based recombinant vaccine. The desired gene (for an antigen) is directly introduced into the genome of the plant chloroplast by using a particle cannon. Most of the currently reported edible vaccines were produced by this method because of the high stability in gene expression. In chloroplasts, many viral antigens like rotavirus and canine parvovirus were expressed. Through overcoat and epic at technologies, several viruses such as cowpea mosaic virus (CPMV), alfalfa mosaic virus, tobacco mosaic virus (TMV), cauliflower mosaic virus (CaMV), tomato bushy stunt virus, and potato virus are designed to express the part of antigenic protein on their surface as reviewed in [95].