Host cell entry receptors for viral vectors

Host cell entry receptors for viral vectors are a diverse group of cell surface molecules, including proteins and carbohydrates, that facilitate the binding and internalization of viral-based gene delivery systems (Pillay et al., 2016 [1]). These receptors are the primary determinants of viral tropism, dictating which tissues and cell types are successfully transduced by vectors such as Adeno-associated virus (AAV), Lentivirus, and Adenovirus (Nayerossadat et al., 2012 [2]). For example, the Adeno-associated virus receptor (AAVR) is a critical host factor for the entry of multiple AAV serotypes, while the Coxsackievirus and adenovirus receptor (CAR) mediates the entry of many adenoviral vectors (Bergelson et al., 1997 [3]). In gene therapy, these receptors are not typically targets for pharmacological inhibition but are essential gateways that must be present on target cells for therapeutic efficacy (Finkelshtein et al., 2013 [4]). The interaction between the viral capsid or envelope and these receptors is exploited by drugs like Onasemnogene abeparvovec to deliver functional genes to motor neurons (Mendell et al., 2017 [5]). Challenges associated with these receptors include their heterogeneous expression across patient populations and the potential for off-target delivery if the receptor is widely expressed in non-target tissues (Wang et al., 2019 [6]). Engineering vectors to target specific receptors or bypass common ones is a major area of research to improve the precision of gene medicine (Mingozzi & High, 2013 [9]).

Other names

Viral entry receptorsViral vector receptorsTransduction receptorsCell surface attachment factors

Viral vectors utilize these receptors to attach to the host cell membrane, triggering receptor-mediated endocytosis or direct membrane fusion to deliver the therapeutic genetic payload into the cell (Maguire et al., 2014 [7]).