Gene Therapy Progress and Prospects: Recombinant adeno-associated virus (rAAV) vectors

Chromatographic purification of recombinant adenoviral and adeno-associated viral vectors: methods and implications

“…84,85 Pseudotyping rAAV vector, that is, using an alternative serotype capsid to package the rAAV vector genome, can also substantially increase the vector transduction efficiency and broaden the host range for rAAV-mediated gene transfer (reviewed by Flotte). 9 Utilization of emerging alternative serotypes and receptor targeted capsid mutants demands the developPurification of adenoviral and AAV vectors E Burova and E Ioffe ment of efficient methods for their production and purification. Affinity purification schemes have been developed for only a subset of the AAV serotypes (eg, heparin resin for AAV2 and mucin resin for AAV-5).…”

“…7,8 Recombinant adeno-associated viral (rAAV) vectors as a class appear to be the most suitable for applications where persistent transgene expression is essential for achieving a therapeutic goal. 9,10 They have a broad host and cell lineage infectivity range for dividing and nondividing cells and are relatively nontoxic. rAAV have a remarkable safety profile; they have not been implicated as the etiological agent for any known disease in human, simian or other species.…”

Long-term correction of murine glycogen storage disease type Ia by recombinant adeno-associated virus-1-mediated gene transfer

“…15 This is a promising start. While AAV2 is not considered pathogenic and has not been implicated in known human diseases, [17][18][19] rAd-mediated gene transfer is associated with inflammation and cellular immune responses. 20,21 We, therefore, sought an improved strategy to avoid these complications.…”

Major role of local immune responses in antibody formation to factor IX in AAV gene transfer

“…Advantages of this vector include absence of viral coding sequences, low innate immunogenicity, production without helper virus, and efficient in vivo gene transfer to nondividing target cells (eg hepatocytes or muscle fibers) with mostly episomal persistence of the vector genome. 6 However, several studies demonstrated formation of antibodies to the F.IX transgene product after AAV-mediated gene transfer. [7][8][9][10][11][12] The risk for such immune responses depended on the underlying F.IX mutation, route of vector administration, vector dose and serotype.…”