Process of delivering small rnas to sperm

Abstract

Methods and compositions directed to altering a population of sRNAs in a sperm using vesicles isolated from an epididymosome are provided. Methods and compositions directed to altering a population of sRNAs in an oocyte using vesicles isolated from an epididymosome are also provided. Methods for altering an sRNA population in a sperm or an oocyte can be used to prevent, or reduce the severity of, a disease, disorder, or condition that would otherwise be inherited by progeny. For example, certain epigenetic inherited conditions due to paternal effects, such as certain metabolic and stress disorders and conditions, can be ameliorated in progeny using sperm or oocytes having an altered sRNA population.

1 - 81 . (canceled) 
     
     
         82 . A pharmaceutical composition comprising an sRNA-containing vesicle isolated from an epididymosome. 
     
     
         83 . The pharmaceutical composition of  claim 82 , wherein the sRNA is selected from the group consisting of a siRNA, a miRNA, a piRNA, a snoRNA, a srRNA, a U-RNA, and a tRNA fragment. 
     
     
         84 . The pharmaceutical composition of  claim 83 , wherein the tRNA fragment is selected from the group consisting of a tRNA-Gly-CCC fragment, a tRNA-Gly-TCC fragment, a tRNA-Gly-GCC fragment, a tRNA-Val-CAC fragment, a tRNA-Glu-CTC fragment, a tRNA-Lys-CTT fragment, and a tRNA-His-GTG fragment. 
     
     
         85 . The pharmaceutical composition of  claim 82 , wherein the pharmaceutical composition is a vaginal foam or a gel. 
     
     
         86 . The pharmaceutical composition of  claim 82 , wherein the epididymosome is selected from the group consisting of caput epididymosome, corpus epididymosome, and cauda epididymosome. 
     
     
         87 . The pharmaceutical composition of  claim 82 , wherein the vesicle comprises a heterologous RNA. 
     
     
         88 . The pharmaceutical composition of  claim 87 , wherein the heterologous RNA comprises a small RNA (sRNA). 
     
     
         89 . The pharmaceutical composition of  claim 88 , wherein the sRNA is selected from the group consisting of a siRNA, miRNA, a piRNA, a snoRNA, a srRNA, a U-RNA, and a tRNA fragment. 
     
     
         90 . The pharmaceutical composition of  claim 89 , wherein the sRNA is a tRNA fragment selected from the group consisting of a tRNA-Gly-CCC fragment, a tRNA-Gly-TCC fragment, a tRNA-Gly-GCC fragment, a tRNA-Val-CAC fragment, a tRNA-Glu-CTC fragment, a tRNA-Lys-CTT fragment, and a tRNA-His-GTG fragment. 
     
     
         91 . The pharmaceutical composition of  claim 82 , wherein the vesicle comprises autologous RNA. 
     
     
         92 . The pharmaceutical composition of  claim 91 , wherein the sRNA is selected from the group consisting of a siRNA, miRNA, a piRNA, a snoRNA, a srRNA, a U-RNA, and a tRNA fragment. 
     
     
         93 . The pharmaceutical composition of  claim 92 , wherein the sRNA is a tRNA fragment selected from the group consisting of a tRNA-Gly-CCC fragment, a tRNA-Gly-TCC fragment, a tRNA-Gly-GCC fragment, a tRNA-Val-CAC fragment, a tRNA-Glu-CTC fragment, a tRNA-Lys-CTT fragment, and a tRNA-His-GTG fragment. 
     
     
         94 . The pharmaceutical composition of  claim 82 , wherein the vesicle comprises an artificial or a synthetic RNA. 
     
     
         95 . The pharmaceutical composition of  claim 94 , wherein the sRNA is selected from the group consisting of a siRNA, miRNA, a piRNA, a snoRNA, a srRNA, a U-RNA, and a tRNA fragment. 
     
     
         96 . The pharmaceutical composition of  claim 95 , wherein the sRNA is a tRNA fragment selected from the group consisting of a tRNA-Gly-CCC fragment, a tRNA-Gly-TCC fragment, a tRNA-Gly-GCC fragment, a tRNA-Val-CAC fragment, a tRNA-Glu-CTC fragment, a tRNA-Lys-CTT fragment, and a tRNA-His-GTG fragment. 
     
     
         97 . The pharmaceutical composition of  claim 82 , wherein the vesicle comprises a transgene. 
     
     
         98 - 141 . (canceled)