Immune responses to viral vectors: implications for neurological gene therapy

ZIRGER; BARCIA; PUNTEL; KROEGER; XIONG; KANG; FAKHOURI; MUHAMMAD; LIU; BERGERON; JOHNSON; CASTRO; LOWENSTEIN

Gene Therapy for neurological disorders

Taylor & Francis

Año: 2006; p. 1 - 16

Gene therapy presents a new approach to alter the consequences of defective geneexpression, and to utilize nucleic acids as therapeutic tools. Over the course of the lastdecade there have been many new techniques that have been developed for the transfer oftherapeutic genes into cells, derived from the modified viruses, or artificial non-viralliposome-based approaches. Non-viral methods have advanced much in the last fewyears; however its efficiency remains below that achieved by virus-derived methods.Viral-derived gene transfer vectors have become reliable tools for gene transfer.Many of the vectors used as vehicles in gene therapy, including the retrovirus,lentivirus, adeno-associated virus and herpes simplex virus are derived from pathogenicviruses, both from humans, as well as other species [1]. Each vector system has itsparticular target tissue. For transduction of continually dividing bone marrow cells, aretroviral or lentiviral vector ought to be used, while for the transduction of terminallydifferentiated muscle or brain cells, adenoviral and AAV-derived vectors are ideal.Lentivirus-derived vectors can transducer both dividing and non-dividing cells, thusmaking this system a choice for the transduction of most organ systems. However, thederivation of these vectors from pathogenic viruses such as HIV, raises concerns on itsacceptance by human patients.Thus, in the absence of one single ideal vector, each vector system has itsparticular target niche. The parent virus, the size of transgenic constructs that can beinserted into different vectors, their intrinsic ease or difficulty of production, theircapacity to infect, express in dividing or non-dividing target cells, all contribute to thechoice of vector.Adenoviral vectors have been shown to provide reliable, efficient, high level ofexpression, following gene transfer into different tissues and organs. Adenoviruses donot cause major lethal diseases, but are effectively neutralized by the humoral andcellular host immune system. This review will focus on the immune response toadenoviral vectors used in the context of gene therapy for the treatment of brain diseases.Immune responses elicited against the other viral vectors used in gene therapyapplications will be discussed elsewhere in this volume.