Abstract
Today, adeno-associated virus (AAV) is an extremely popular choice for gene therapy delivery. The safety profile and simplicity of the genome organization are the decisive advantages which allow us to claim that AAV is currently among the most promising vectors. Several drugs based on AAV have been approved in the USA and Europe, but AAV serotypes’ unspecific tissue tropism is still a serious limitation. In recent decades, several techniques have been developed to overcome this barrier, such as the rational design, directed evolution and chemical conjugation of targeting molecules with a capsid. Today, all of the abovementioned approaches confer the possibility to produce AAV capsids with tailored tropism, but recent data indicate that a better understanding of AAV biology and the growth of structural data may theoretically constitute a rational approach to most effectively produce highly selective and targeted AAV capsids. However, while we are still far from this goal, other approaches are still in play, despite their drawbacks and limitations.
Highlights
Gene therapy (GT) is a relatively novel and promising branch of biomedicine which is based on the delivery of a transgene encoding either therapeutic protein or RNA
The present review shows the most useful and effective approaches for associated virus (AAV) tropism modification: rational design, directed evolution and chemical conjugation
A huge amount of work devoted to AAV tropism modification succeeded in the construction of novel AAV
Summary
Gene therapy (GT) is a relatively novel and promising branch of biomedicine which is based on the delivery of a transgene encoding either therapeutic protein or RNA. Different viral vectors have different cell tropisms, genome capacities and safety profiles; different viruses could potentially be used for targeted delivery. Modern research in this area is focused mostly on retroviruses, adenoviruses and adeno-associated viruses [1]. In comparison to the viral vectors listed above, adeno-associated viruses (AAVs) have a better safety profile This is crucial for the successful clinical application of gene therapy. AAV genome capacity is 4.8 kilobases, which is lower in comparison to other vectors; it is unable to replicate viral DNA on its own, so it is preferable to use AAV for the targeting of slowly dividing cells, for example, fibroblast-like synoviocytes (FLSs) and macrophage-like synoviocytes (MLSs), which are considered to be promising targets for rheumatoid arthritis gene therapy [7]. This review summarizes different approaches of AAV retargeting and tropism modifications, their limitations, accomplishments and several difficulties that may be faced by anyone who decides to alter the AAV structure to generate a selective GT
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