Local delivery of viral vectors
Delivery of viral vector therapeutics to certain areas of the body helps enhance transgene expression in a localized area in gene therapy and improves therapeutic impact in drug delivery. Viral vectors can be used for therapeutics, such as gene therapy, by inserting genetic material or drugs into cells to help treat patients. There are a variety of technologies and methods to locally deliver these viral vectors and target certain tissues to help improve the vectors’ life-time, efficacy, and minimize adverse side-effects.[1]
Viral Vector for Gene Therapy Overview
Viral vectors are created by removing the genetic material from viruses. Viral vectors can be created from retroviruses, lentivirus, adenovirus, and adeno-associated virus. For gene therapy, the genetic code for the gene of interest is put into the viral capsid. These viral vectors are then used to deliver the genetic material into cells in the body to initiate gene expression in host tissues.[2]
Benefits of Local Delivery
Viral vector gene therapy is generally done by directly injecting the vectors into the body. This drug delivery method is associated with some limitations. There is systemic spread of the vectors throughout the body. This can lead to gene expression in off-target tissues and increased immune reactions. By using strategies to localize the viral vector gene therapy delivery, it is possible to increase gene expression in a certain area or tissues of the body with the goal of increasing the duration of gene expression and reducing immune-related effects.[2][3]
Methods of local delivery
There are many methods to localize viral vectors for gene therapy in the body ranging from encapsulating them in biomaterials to altering the chemical composition of the viral capsid.[2] This article will discuss various methods that have been studied to target delivery of viral vectors.
Local Injection
The simplest way to locally deliver viral vectors is to inject them into the body in the location of desired gene expression rather than deliver them systemically. For instance, scientists can do intratumoral injections to treat cancer with gene therapy.[4] A study found that local delivery to the liver in rabbits decreased immune reactions while causing most of the gene expression to be in the targeted tissues. [5]
Hydrogels and Scaffolds
Scaffolds loaded with viral vectors can be created with varying pore sizes in order to control the release rate of the vectors into the body and help localize the treatment to the tissues around the location that the scaffold is placed in.[2] Hydrogels have many drug delivery applications, and they have been used to help locally deliver viral vectors in the body. Gels have been shown to be able to adhere to places in the body and help deliver viral vectors to the surface of organs.[6] One example of hydrogels and scaffolds to deliver viral vectors locally is fibrin scaffolds that released viral vectors to help cartilage repair. Scaffolds were tested with varying characteristics to determine which had the best gene transfer efficiency.[7] By combining other chemicals or components into scaffolds scientists have been able to specifically target certain cell types, for instance a PLG/HAp scaffold with viral vectors preferentially transduced non-immune cells in comparison to PLG scaffolds.[8] One challenge associated with using scaffolds is a large initial burst release of the vectors from the scaffold. [2] Scientists have been able to alter the scaffold to increase the retention of the viral vectors; for instance, chitosan and heparin in PLG scaffolds was shown to improve the association and transduction of the viral vectors to help treat spinal cord injuries.[9]
Metal Surfaces
Viral vectors can also be attached to metal surfaces in the body, such as stents, pins, rods, etc. Scientists have been able to show how to attach the viral vectors to the metal, and how in murine models, it caused localized delivery and gene expression in the tissues around the implant.[10] Scientists have used stents to locally deliver viral vectors to decrease in-stent restenosis.[11]
Magnetofection
Magnetofection involves using magnetic fields to cause particles with vectors to enter targeted cells. Magnetic nanoparticles with viral vectors can utilize magnetofection to help increase gene expression in localized areas of the body. Scientists were able to create magnetic nanoparticles that bind to a certain cell type, K652 cells, in the presence of magnetic fields which helped increase gene expression in those cells.[12]
Surface Engineering
One method for localized delivery of viral vectors is chemically altering the viral capsid surface. Viral vectors can be encapsulated in other materials or covalently conjugated with certain materials.[3] One example of altering the surface is that scientists created a viral vector with ‘tLyP-1” on the surface which targets and binds to tumors and delivers encapsulated drugs to kill the tumor.[13]
References
- ↑ Kasala, D (2016). "Evolving lessons on nanomaterial-coated viral vectors for local and systemic gene therapy". Nanomedicine. 11 (13): 1689–1713. doi:10.2217/nnm-2016-0060. PMC 5561791. PMID 27348247.
- ↑ 2.0 2.1 2.2 2.3 2.4 Jang, J. (2011). "Engineering biomaterial systems to enhance viral vector gene delivery". Molecular Therapy : The Journal of the American Society of Gene Therapy. 19 (8): 1407–1415. doi:10.1038/mt.2011.111. PMC 3149164. PMID 21629221.
- ↑ 3.0 3.1 Kasala, D (2021). "Overcoming the barriers to optimization of adenovirus delivery using biomaterials: Current status and future perspective". Journal of Controlled Release. 332 (168–3659): 285–300. doi:10.1016/j.jconrel.2021.02.018. PMID 33626335 Check
|pmid=value (help). Unknown parameter|s2cid=ignored (help) - ↑ Wang, Y (2003). "Systemic dissemination of viral vectors during intratumoral injection". Molecular Cancer Therapy. 2 (11): 1233–1242. PMID 14617797.
- ↑ Hodges, B (2005). "Local Delivery of a Viral Vector Mitigates Neutralization by Antiviral Antibodies and Results in Efficient Transduction of Rabbit Liver". Molecular Therapy. 12 (6): 1043–1051. doi:10.1016/j.ymthe.2005.06.475. PMID 16139571.
- ↑ Carolina, J (2019). "Adhesive thermosensitive gels for local delivery of viral vectors". Biotechnology and Bioengineering. 116 (9): 2353–2363. doi:10.1002/bit.27007. PMC 7001463 Check
|pmc=value (help). PMID 31038193. - ↑ Lee, H (2011). "Release of bioactive adeno-associated virus from fibrin scaffolds: Effects of fibrin glue concentrations". Tissue Engineering. 17 (15–16): 1969–1978. doi:10.1089/ten.tea.2010.0586. PMC 3142631. PMID 21449684.
- ↑ Boehler, R (2013). "A PLG/HAp composite scaffold for lentivirus delivery". Biomaterials. 34 (21): 5431–5438. doi:10.1016/j.biomaterials.2013.04.009. PMC 3653272. PMID 23602363.
- ↑ Thomas, A (2013). "Polysaccharide-modified scaffolds for controlled lentivirus delivery in vitro and after spinal cord injury". Journal of Controlled Release. 170 (3): 421–429. doi:10.1016/j.jconrel.2013.06.013. PMC 3742643. PMID 23791981.
- ↑ Pressly, B (2022). "Adeno-associated viral vector immobilization and local delivery from bare metal surfaces". Biomedical Engineering Technologies. Methods in Molecular Biology. 2394. pp. 601–616. doi:10.1007/978-1-0716-1811-0_32. ISBN 978-1-0716-1810-3. PMID 35094349 Check
|pmid=value (help). Unknown parameter|s2cid=ignored (help) Search this book on
- ↑ Fishbein, I (2017). "Stent-based delivery of adeno-associated viral vectors with sustained vascular transduction and iNOS-mediated inhibition of in-stent restenosis". Gene Therapy. 24 (11): 717–726. doi:10.1038/gt.2017.82. PMC 5709213. PMID 28832561.
- ↑ Bhattarai, Shanta (2008). "N-hexanoyl chitosan-stabilized magnetic nanoparticles: enhancement of adenoviral-mediated gene expression both in vitro and in vivo". Nanomedicine: Nanotechnology, Biology and Medicine. 4 (2): 146–154. doi:10.1016/j.nano.2008.02.001. PMID 18374634.
- ↑ Ghosh, S (2021). "A smart viral vector for targeted delivery of hydrophobic drugs". Scientific Reports. 11 (7030): 7030. Bibcode:2021NatSR..11.7030G. doi:10.1038/s41598-021-86198-y. PMC 8007742 Check
|pmc=value (help). PMID 33782428 Check|pmid=value (help).
This article "Local delivery of viral vectors" is from Wikipedia. The list of its authors can be seen in its historical and/or the page Edithistory:Local delivery of viral vectors. Articles copied from Draft Namespace on Wikipedia could be seen on the Draft Namespace of Wikipedia and not main one.
