The state of the art of adeno-associated virus-based vectors in gene therapy

Abstract

The adeno-associated virus (AAV) has rapidly gained popularity in gene therapy since the establishment of the first AAV2 infectious clone, in 1982, due to some of their distinguishing characteristics such as lack of pathogenicity, wide range of infectivity, and ability to establish longterm transgene expression. Notably over the past decade, this virus has attracted considerable interest as a gene therapy vector, and about 85% of the currently available 2,041 PubMed references on adeno-associated viruses have been published during this time. The exponential progress of AAV-based vectors has been made possible by the advances in the knowledge of the virology and biology of this virus, which allows great improvement in AAV vectors construction and a better comprehension of their operation. Moreover, with the recent discovery of novel AAV serotypes, there is virtually one preferred serotype for nearly every organ or tissue to target. Thus, AAV-based vectors have been successfully overcoming the main gene therapy challenges such as transgene maintenance, safety and host immune response, and meeting the desirable vector system features of high level of safety combined with clinical efficacy and versatility in terms of potential applications. Consequently, AAV is increasingly becoming the vector of choice for a wide range of gene therapy approaches. This report will highlight the state of the art of AAV-based vectors studies and the advances on the use of AAV vectors for several gene therapy approaches.

Enhancement of recombinant adeno-associated virus mediated transgene expression by targeted echo-contrast agent

“…Exchanging capsids between various AAV serotypes is effective for conferring specific cellular tropism and intensity, as well as onset of gene expression (Coura and Nardi, 2007;Surace and Auricchio, 2008). Virus-mediated gene delivery has resulted in higher levels of cardiac transduction (about 30-to 360-fold) compared to plasmid approaches after direct intramyocardial injections in rabbits (Wright et al, 2001).…”

siRNA Therapeutic Design: Tools and Challenges

“…Viral-based delivery can be achieved using adenoviruses (ADs), adeno-associated viruses (AAVs), or retroviruses such as lentiviruses (Ghosh et al 2006;Coura and Nardi 2007;Cockrell and Kafri 2007). ADs are large viruses (60-90 nm in diameter) and are typically transported into the cell through clathrin-coated endocytosis (Ghosh et al 2006).…”

Viral Vectors in Neurobiology: Therapeutic and Research Applications

“…These vectors do offer some advantages over other vector systems which include the lack of initiating an immune response, their stability and ability to infect a variety of dividing and non-dividing cells. Unfortunately, they cannot incorporate genes larger than 5 kb and must be closely screened for adenoviral or HSV contamination (Berns, 1996;Grimm & Kay, 2003;Coura & Nardi, 2007;Coura & Nardi, 2008;Mezzina & Merten, 2011). …”

“…Current studies have been leading to great improvements in AAV vector and expression cassette design and novel AAV serotypes have been identified, that have improved AAV vectors efficacy (Kaspar et al, 2002;Coura & Nardi, 2007;McCown, 2011).…”