GET protocols: Hyaluronidase is an effective adjuvant in the permeabilization of muscle fibers

OLAIZ NAHUEL; SIGNORI EMANUELLA; GUERRA LILIANA; MAGLIETTI FELIPE; SUÁREZ CECILIA; VILLAVERDE MARCELA; COLOMBO LUCAS; MICHINSKI SEBASTIÁN; MARSHALL GUILLERMO

Portoroz

Congreso; 1st World Congress on Electroporation and Pulsed Electric Fields in Biology, Medicine and Food & Environmental Technologies; 2015

COST TD1104 Action

p { margin-bottom: 0.25cm; direction: ltr; color: rgb(0, 0, 0); line-height: 120%; text-align: left; widows: 2; orphans: 2; }p.western { font-family: "Calibri",serif; font-size: 11pt; }p.cjk { font-family: "Calibri"; font-size: 11pt; }p.ctl { font-family: "Times New Roman",serif; font-size: 11pt; }Since 1950, hyaluronidase has been known as a ?spreading factor?favoring better diffusion of traditional vaccines in the site ofinoculation. Nowadays, hyaluronidase is used in the clinical practiceas adjuvant therapy to increase the absorption and dispersion ofinjected drugs. In our laboratory we are evaluating the optimalconditions for effective gene electrotransfer (GET) protocols for thedelivery of plasmid vectors. We have theoretically predicted by insilico modeling that optimal efficiency in GET protocols could beachieved when the applied electric field is near 158 V/cm, usinghyaluronidase as an adjuvant [1]. Here, we evaluated in vivo ourprevious theoretical predictions. Our results show that: a) thepresence of pH fronts in mice skins when electric fields are appliedis experimentally corroborated; b) enhanced level of the expressionvector in tissues pretreated with hyaluronidase and electric fields>150 V/cm is experimentally corroborated; c) evidence thatelectric fields between 150 and 200 V/cm would be optimal for GETprotocols based on pretreatment with hyaluronidase is experimentallycorroborated; d) the presence of tissue damage when the electricfield applied is near 200 V/cm is experimentally corroborated; e)theoretical predictions from [1] are experimentally corroborated. p { margin-bottom: 0.25cm; direction: ltr; color: rgb(0, 0, 0); line-height: 120%; text-align: left; widows: 2; orphans: 2; }p.western { font-family: "Calibri",serif; font-size: 11pt; }p.cjk { font-family: "Calibri"; font-size: 11pt; }p.ctl { font-family: "Times New Roman",serif; font-size: 11pt; }ince 1950, hyaluronidase has been known as a ?spreading factor?favoring better diffusion of traditional vaccines in the site ofinoculation. Nowadays, hyaluronidase is used in the clinical practiceas adjuvant therapy to increase the absorption and dispersion ofinjected drugs. In our laboratory we are evaluating the optimalconditions for effective gene electrotransfer (GET) protocols for thedelivery of plasmid vectors. We have theoretically predicted by insilico modeling that optimal efficiency in GET protocols could beachieved when the applied electric field is near 158 V/cm, usinghyaluronidase as an adjuvant [1]. Here, we evaluated in vivo ourprevious theoretical predictions. Our results show that: a) thepresence of pH fronts in mice skins when electric fields are appliedis experimentally corroborated; b) enhanced level of the expressionvector in tissues pretreated with hyaluronidase and electric fields>150 V/cm is experimentally corroborated; c) evidence thatelectric fields between 150 and 200 V/cm would be optimal for GETprotocols based on pretreatment with hyaluronidase is experimentallycorroborated; d) the presence of tissue damage when the electricfield applied is near 200 V/cm is experimentally corroborated; e)theoretical predictions from [1] are experimentally corroborated. p { margin-bottom: 0.25cm; direction: ltr; color: rgb(0, 0, 0); line-height: 120%; text-align: left; widows: 2; orphans: 2; }p.western { font-family: "Calibri",serif; font-size: 11pt; }p.cjk { font-family: "Calibri"; font-size: 11pt; }p.ctl { font-family: "Times New Roman",serif1950, hyaluronidase has been known as a ?spreading factor?favoring better diffusion of traditional vaccines in the site ofinoculation. Nowadays, hyaluronidase is used in the clinical practiceas adjuvant therapy to increase the absorption and dispersion ofinjected drugs. In our laboratory we are evaluating the optimalconditions for effective gene electrotransfer (GET) protocols for thedelivery of plasmid vectors. We have theoretically predicted by insilico modeling that optimal efficiency in GET protocols could beachieved when the applied electric field is near 158 V/cm, usinghyaluronidase as an adjuvant [1]. Here, we evaluated in vivo ourprevious theoretical predictions. Our results show that: a) thepresence of pH fronts in mice skins when electric fields are appliedis experimentally corroborated; b) enhanced level of the expressionvector in tissues pretreated with hyaluronidase and electric fields>150 V/cm is experimentally corroborated; c) evidence thatelectric fields between 150 and 200 V/cm would be optimal for GETprotocols based on pretreatment with hyaluronidase is experimentallycorroborated; d) the presence of tissue damage when the electricfield applied is near 200 V/cm is experimentally corroborated; e)theoretical predictions from [1] are experimentally corroborated.