GENE SILENCING IN SKIN USING SELF-DELIVERY siRNA DELIVERED BY A MESO DEVICE

Abstract

The present invention is drawn to a low-cost “meso” device that is able to effectively deliver functional self-delivery siRNA to subject and inhibit expression of a gene in the subject as well as related methods. In particular, a method of transdermally delivering nucleic acid material to a subject is provided. The method includes adapting a motorized meso machine for delivery of nucleic acid material; introducing nucleic acid material into a chamber of the motorized meso machine; and contacting the motorized meso machine to a skin surface of a subject for a period of time sufficient to deliver the nucleic acid material into the skin surface of the subject.

1 . A method for delivering nucleic acid material for treatment of a monogenic skin disorder, the method comprising:
 introducing a nucleic acid material into a chamber of a motorized meso machine, the motorized meso machine comprising microneedles operatively coupled to the chamber;   contacting the microneedles of the motorized meso machine to a skin surface of a subject in need of the treatment; and   actuating the motorized meso machine such that the microneedles are inserted into the skin surface of the subject for a period of time for delivering a therapeutically effective dose of the nucleic acid material from the chamber into the skin surface of the subject.   
     
     
         2 . The method of  claim 1 , wherein the nucleic acid material comprises siRNA or sd-siRNA configured to silence a gene, a mutation in which results in the monogenic disorder. 
     
     
         3 . The method of  claim 1 , wherein the monogenic disorder is pachyonychia congenita. 
     
     
         4 . The method of  claim 5 , wherein the nucleic acid material comprises TD101 siRNA. 
     
     
         5 . The method of  claim 1 , wherein the steps of contacting the microneedles and actuating the motorized meso machine are repeated periodically on a same area on the skin surface so as to periodically deliver the nucleic acid material to the same area. 
     
     
         6 . The method of  claim 1 , wherein step of contacting the microneedles and actuating the motorized meso machine are repeated on an adjacent skin area so as to deliver the nucleic acid material to the adjacent skin area. 
     
     
         7 . The method of  claim 1 , wherein the microneedles are configured to deliver the nucleic acid material into the skin surface at a depth in a range from 25 μm to 3 mm. 
     
     
         8 . The method of  claim 1 , wherein the period of time is at about 5 seconds to about 20 seconds. 
     
     
         9 . The method of  claim 1 , wherein the subject is a human. 
     
     
         10 . The method of  claim 1 , further comprising adjusting, following an insertion of the microneedles into the skin surface, a rate of oscillation of the microneedles by the motorized meso machine. 
     
     
         11 . A device for treatment of a monogenic skin disorder, the device comprising:
 a motorized meso machine having:   a chamber configured to contain a volume of a the nucleic acid material; and   microneedles operatively coupled to the chamber such that upon contacting the microneedles to a skin surface of a subject and actuating the motorized meso machine for a period of time, the nucleic acid material flows from the chamber onto the skin surface and the microneedles are inserted into the skin surface to deliver a predetermined volume of the nucleic acid material from the chamber into the skin surface of the subject at a predetermined depth.   
     
     
         12 . The device of  claim 11 , wherein the device is configured to oscillate the microneedles at an adjustable a rate of oscillation. 
     
     
         13 . The device of  claim 11 , wherein microneedles have a length in a range from 25 μm to 3 mm. 
     
     
         14 . The device of  claim 11 , wherein the predetermined depth to which the nucleic acid material is delivered is in a range from 25 μm to 3 mm. 
     
     
         15 . The device of  claim 11 , wherein the predetermined volume is in a range from 10 μl to 500 μl. 
     
     
         16 . The device of  claim 11 , wherein the period of time is in a range from 5 seconds to 20 seconds. 
     
     
         17 . The device of  claim 11 , wherein the nucleic acid material comprises a nucleic acid and an indicator. 
     
     
         18 . The device of  claim 11 , wherein the subject is a mammal. 
     
     
         19 . The device of  claim 11 , wherein the nucleic acid material comprises siRNA or sd-siRNA. 
     
     
         20 . The device of  claim 11 , wherein the nucleic acid material is suspended in a solution comprising a phosphate buffer.