Scheme 1

Depicting the ‘sensitization period’.

Depicting the ‘sensitization period’. The scheme describes a discrete window of time characterized as a sensitization period that occurs from 5 to 72 hours following an i.t. pretreatment (also referred to as a first i.t. injection) of pDNA. During the sensitization period, an accumulation of leukocytes occurs surrounding the i.t. injection site. A possible mechanism underlying transgene therapeutic efficacy following this double-injection paradigm may be that accumulated peri-spinal leukocytes are induced to express an anti-inflammatory pro-phagocytic activation profile following the initial injection resulting in improved phagocytosis of subsequently delivered transgene.