Ultrasound as a platform for formulation and sequence-independent delivery of nucleic acids

PROJECT SUMMARY The development of nucleic acids as therapeutics continues to gain significant attention as a promising opportunity for the treatment of many diseases given their ability to alter gene expression with a high degree of specificityThere are a multitude of candidates in clinical developmentbut they largely target diseases of the liver because of the body s natural clearance of material to that organIndeedthe inability to deliver nucleic acids to multiple areas of the body has stymied their broad clinical developmentNucleic acid therapeutics may be especially efficacious for treating acute diseases given their ability to precisely modulate gene expressionOne such disease is oral mucositisa debilitating and treatment altering side effect of chemotherapy and radiationGiven the acute nature of this diseasethe capacity to deliver nucleic acid therapeutics locally in the oral cavity may prove prophylactic in preventing the onset of mucositis entirelyA technology enabling local administration of nucleic acids independent of formulation or sequence would prove invaluable for the treatment of a myriad of diseases outside of the liverincluding oral mucositisSuono Bio s long term goal is to develop therapeutic products leveraging our novel platform delivery technology that enables formulation and sequenceindependent delivery of nucleic acids throughout the body to address a wide range of diseases with high unmet needThe overall objective of this applicationwhich is the next step toward attainment of our long term goalis to demonstrate the functional delivery in vivo of a broad range of unformulated nucleic acids using our lead clinical form factorthe Suonofor local delivery in the oral cavity and to screen and identify in a preclinical model of oral mucositis a lead nucleic acid therapeutic for further clinical developmentThe rationale for this project is the use of low frequency ultrasound technology to physically propel nucleic acids into tissue independent of formulationachieving rapidlocal delivery while enhancing bioavailabilityIn Aimwe will investigate the depth of penetration and define transfected cells following the delivery of two different naked mRNAs with different sequence lengths in vivo using the SuonoIn Aimwe will build on this capacity by investigating the preclinical efficacy of different types of nucleic acids in combination with the Suonoin a hamster cheek model of oral mucositisThe proposed research is innovative as it utilizes low frequency ultrasound to enable formulationand sequence independent delivery of a broad range of nucleic acidsobviating the need for tedious optimization of the therapeuticIts successful completion will broadly demonstrate the capacity of the core technology to facilitate rapidformulation independent delivery of nucleic acid therapeutics and identify a lead nucleic acid therapeutic for further development for the treatment of oral mucositis PROJECT NARRATIVE Nucleic acid based therapeutics hold tremendous promise for not only treating but potentially curing a myriad of diseases with high unmet needhoweverdelivery of nucleic acids remains a significant challenge to their use clinicallyThis proposal aims to develop a platform delivery system capable of ultra rapid delivery of nucleic acids independent of formulation or sequence and apply this technology for the treatment of oral mucositisa debilitating diseaseThis technology will impact clinical practice by expediting the translation of these therapies to the clinicreducing the need for tedious formulation development