Transcriptome transfer produces cellular phenotype conversion

Abstract

The present invention includes methods for effecting phenotype conversion in a cell by transfecting the cell with phenotype-converting nucleic acid. Expression of the nucleic acids results in a phenotype conversion in the transfected cell. Preferably the phenotype-converting nucleic acid is a transcriptome, and more preferably an mRNA transcriptome.

1 . A method of effecting phenotype conversion in a cell, said method comprising transfecting phenotype-converting nucleic acid of a first cell having a phenotype into a second cell having a phenotype, wherein the phenotype of said first cell is different from the phenotype of said second cell, and wherein said transfected phenotype-converting nucleic acid causes the phenotype of said second cell to change to the phenotype of said first cell. 
     
     
         2 . The method of  claim 1 , wherein said phenotype-converting nucleic acid is an mRNA transcriptome. 
     
     
         3 . The method of  claim 1 , wherein said phenotype of said first cell differs from said phenotype of said second cell by one or more of: species, tissue type, differentiation degree, disease state, exposure to a toxin, exposure to a pathogen, and exposure to a candidate therapeutic. 
     
     
         4 . The method of  claim 1 , wherein said mRNA transcriptome comprises mRNA transcripts having an average size between about 1 kb to about 5 kb. 
     
     
         5 . The method of  claim 1 , further comprising transfecting said second cell at least a second time with said first cell mRNA transcriptome. 
     
     
         6 . The method of  claim 1 , wherein said transfecting step comprises irradiating said cell with a laser, wherein said cell is bathed in a fluid comprising said first cell mRNA transcriptome. 
     
     
         7 . The method of  claim 6 , wherein said irradiating step comprises 2 to 25 laser excitation pulses, wherein said laser is directed to different site on said second cell for each laser excitation pulse. 
     
     
         8 . The method of  claim 1 , wherein said second cell is contacted with an exogenous transcription inhibition agent prior to said transfecting step. 
     
     
         9 . The method of  claim 1 , wherein said second cell is not substantially contacted with an exogenous transcription inhibition agent before, during or after said transfecting step. 
     
     
         10 . The method of  claim 1 , wherein said cell is selected from the group consisting of a eukaryotic cell and a prokaryotic cell. 
     
     
         11 . The method of  claim 10 , wherein said eukaryotic cell is a non-mammalian cell. 
     
     
         12 . The method of  claim 10 , wherein said eukaryotic cell is a mammalian cell. 
     
     
         13 . The method of  claim 12 , wherein said eukaryotic cell is a human cell. 
     
     
         14 . The method of  claim 2 , wherein said phenotype-converting nucleic acid further comprises one or more exogenous nucleic acids selected from the group consisting of mRNA, siRNA, miRNA, hnRNA, tRNA, non-coding RNA and combinations thereof. 
     
     
         15 . The method of  claim 1 , wherein said phenotype conversion comprises a change in one or more of gene expression, protein expression, immunological markers, morphology, physiology, synthesis of bioproducts, and membrane lipid composition. 
     
     
         16 . The method of  claim 15 , wherein phenotype conversion comprises a change in expression of at least 100 genes. 
     
     
         17 . The method of  claim 15 , wherein phenotype conversion comprises up-regulation of genes associated with chromosomal remodeling. 
     
     
         18 . The method of  claim 15 , wherein at least about 5% of differentially expressed genes in said second cell change expression to a level observed for said first cell. 
     
     
         19 . The method of  claim 1 , wherein said phenotype conversion persists for at least 2 weeks. 
     
     
         20 . The method of  claim 19 , wherein said phenotype conversion persists for the lifetime of the cell. 
     
     
         21 . The method of  claim 1 , wherein the second cell is a hair cell that responds to a first range of sound frequencies. 
     
     
         22 . The method of  claim 21 , wherein the first cell is a hair cell that responds to a second range of sound frequencies. 
     
     
         23 - 26 . (canceled)