Production of Retroviral and Lentiviral Gene Therapy Vectors: Challenges in the Manufacturing of Lipid Enveloped Virus

摘要: Gamma-retroviral vectors, commonly designated retroviral were the first viral vector employed in Gene Therapy clinical trials 1990 and are still one of most used. More recently, interest lentiviral derived from complex retroviruses such as human immunodeficiency virus (HIV), has been growing due to their ability transduce non-dividing cells (Lewis et al. 1992; Naldini 1996), an attribute that distinguishes them other including simple counterparts, gammaretroviral vectors. Retroviral vectors attractive features gene transfer tools include capacity for large genetic payload (up 9 kb), minimal patient immune response, high transducing efficiency vivo vitro, permanently modify content target cell, sustaining a long-term expression delivered (Coroadinha 2010; Schweizer Merten 2010). According recent updates, represent 23% all types 33% used trials. Moreover, currently blockbuster treatment monogenic infectious diseases marking (Edelstein Retroviruses double stranded RNA enveloped viruses mainly characterized by “reverse-transcribe” genome DNA. Virions measure 100-120 nm diameter contain dimeric identical positive strands complexed with nucleocapsid (NC) proteins. The is enclosed proteic capsid (CA) also contains enzymatic proteins, namely reverse transcriptase (RT), integrase (IN) proteases (PR), required infection. matrix proteins (MA) form layer outside core interacts envelope, lipid bilayer host cellular membrane, which surrounds particle (Coffin 1997). Anchored on this bilayer, envelope glycoproteins (Env) responsible recognizing specific receptors cell initiating infection process. Envelope formed two subunits, transmembrane (TM) anchors protein into membrane surface (SU) binds (Fig. 1).