Viral vectors have played a significant role in the evolution of gene therapies over the past few years, and in the field of gene transfer, lentivirus (LV) and adeno-associated virus (AAV) vectors are becoming more common.
According to research that was published in Signal Transduction and Targeted Therapy, vectors are currently used in approximately half of all clinical trials that are related to vectors. Adenoviruses, a mainstay of research with concerns about immunogenicity, make up the other half.
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In comparison to adenoviruses, AAV and LV vectors can be desirable options for researchers working with viral vectors. They can both infect dividing and nondividing cells, and there is also less risk of a significant immune response from the host.
Although they are similar, their differences have an impact on applications and workflows, particularly in terms of purity and viability.
The pros and cons of adeno-associated virus vectors
An AAV is a dependoparvovirus that typically depends on an adenovirus or another helper virus for the expression of its genetic material. An AAV vector is particularly advantageous as a transfer mechanism for gene therapies involving the heart, liver, and central nervous system due to its extensive viral tropism profile, according to Signal Transduction and Targeted Therapy.
However, AAVs are not always the best option, particularly for in vitro research. The in vivo response to transduction behavior is not always predictable in vitro; this needs to be studied further using nonhuman primates before clinical trials can be conducted. AAV vectors have a maximum package size of about five kilobases, which is another restriction.
The pros and cons of Lentiviral vectors
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As a subtype of retrovirus, LV vectors — such as those derived from HIV — are renowned for their capacity to express multiple genes as well as their capacity to integrate within the genome.
They are also amenable to in vitro research. Due to these benefits, LV vectors are frequently used to treat complex disease states like congenital diseases, immune and metabolic disorders, and cancers.
However, as noted in Signal Transduction and Targeted Therapy, third-generation, self-inactivating LV vectors can reduce the risk of insertional mutagenesis, which LV vectors have historically carried.
Purification and viability of adeno-associated virus and lentiviral vectors
The downstream purification requirements for AAV and LV vectors differ depending on the type of vehicle, but there are also safety and operational challenges. AAVs typically require cellular lysis, which can leave contaminants behind from host cells, as mentioned in Scientific Reports.
Incomplete and empty viral capsids are common during the production of AAV vectors, and these can pose a risk of contamination. On the other hand, LV vectors could require a more involved or restrictive processing workflow to reach desired yield and purity,
Researchers are increasingly using closed and semi-automated systems for bioburden and processing control as a result of these and other concerns.
Automation tools built into these systems lessen the need for manual handling and processing, which lowers the risk of AAV vector contamination and meets workflow requirements for LV vectors. Closed systems can lessen the dangers of environmental contamination.
According to Cell Culture Dish, researchers are also considering high-yield adherent culture platforms, such as Corning CellSTACK® culture chambers and HYPERStack® vessels, which can facilitate more effective scale-up.
These items, along with the next-generation fixed-bed bioreactors like the Corning Ascent® Fixed Bed Reactor, increase scale potential and provide automated control in closed systems while having a larger surface area to volume ratio in a smaller footprint.
Finding what works for the user
Every tool has a set of ideal applications. Similar to other gene transfer mechanisms, AAV and LV vectors have benefits, drawbacks, and scaling considerations. Thankfully, there are now options for researchers, and the more progress made in gene therapies, the more optimistic the future appears to be for patients who require them.
About Corning Life Sciences
A division of Corning Incorporated, Corning Life Sciences is a leading global manufacturer of cell culture products and solutions that enable academic, biotech and biopharma scientists to harness the power of cells to create life-changing innovations. Corning supports a range of application areas including core cell culture, 3D cell culture, bioprocess, cancer research, primary and stem cell research, drug screening, cell and gene therapy, disease modeling, lab automation and more.
Whether your goal is stem cell expansion or viral vector production, Corning Life Sciences platforms, including HYPERStack® vessels that maximize cell growth area in a small footprint, the high-yield Ascent® Fixed Bed Reactor platform, microcarriers, and closed system solutions can help get you there. Choose from hundreds of vessels, the widest selection of cell culture surfaces, and custom media in a variety of single-use technology configurations. Learn more at www.corning.com/lifesciences.