I must be reading it wrong. It's using a harmless virus to modify mRNA. Please explain?
"Exons’ genetic information is transcribed into an intermediate molecule called messenger RNA (mRNA) that is used to guide protein production. Exons are translated and, much like with a puzzle, pieced together in the mRNA molecule.
…
Researchers at the Nationwide Children’s Hospital, in Ohio, developed an exon skipping therapy that uses a modified and harmless virus, called scAAV9.U7-ACCA, to deliver the genetic sequence of four molecules designed to force exon 2 skipping in the DMD gene’s mRNA. The one-time therapy is given directly into the bloodstream."
This therapy uses genetic material but not mRNA; however mRNA is the target. This therapy introduces DNA that encodes non-coding RNA. It is then this non-coding RNA that targets the DMD gene mRNA.
It looks like it doesn’t modify DNA, but it does modify what was just transcribed from the gene by removing an exon from the corresponding mRNA that came from the gene.
The source describes the 4 molecules the virus injects:
We developed a therapeutic exon skipping viral vector (scAAV9.U7-ACCA) comprising four copies of a modified U7snRNA containing antisense sequences targeting the splice donor (2 copies) and splice acceptor (2 copies) of the DMD exon 2, the most commonly duplicated exon.
The definition of a gene from bleh wikipedia is: "A gene is a region of DNA that encodes function." And it goes on to say: "During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function."
For exon: "An exon is any part of a gene that will encode a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term exon refers to both the DNA sequence within a gene and to the corresponding sequence in RNA transcripts. In RNA splicing, introns are removed and exons are covalently joined to one another as part of generating the mature messenger RNA [mRNA]. Just as the entire set of genes for a species constitutes the genome, the entire set of exons constitutes the exome."
So, where I'm trying to go with this and what I'm trying to understand is, if muscular distrophy is a genetic disorder caused by a genetic mutation that causes a lack of a protein called dystrophin, and they're testing this gene therapy to fix a genetic mutation by modifying genes to produce more dystrophin, then how is that not modifying DNA? Is it because they're modifying the virus RNA to inject it's genes into a human, and so it's technically the virus that's modifying genes, hence DNA? From my understanding, an exon is a small section of a gene, and a gene is a small section of DNA.
Doing more research, is it because they're modifying mRNA to force it to make the dystrophin protein? mRNA is supposed to copy itself in the transcription process from DNA, and then use this copy to make proteins, or whatever it's function is. So, they're manipulating this DNA copy, the mRNA, to force it to produce the protein they want? How does it know when to stop?
Isn't this what the mRNA COVID vaccines are doing? Or am I way off?
From reading the source doc https://mdaconference.org/node/1150 , the scientists put 4 modified snRNA molecules into a virus to deliver into the cell.
From reading the main article, 11% of DMS sufferers have an issue with duplicate exon 2s. From basic biochemistry, when the mRNA with the extra exon 2 gets translated by the ribosome into dystrophin, the resulting dystrophin protein doesn’t work.
The 4 snRNA molecules per the main article prevent the extra exon 2s from being connected into the mRNA resulting in an mRNA that gets translated into a functioning dystrophin protein.
So there is no modification of the DNA, only the resulting mRNA that was transcribed from the DNA (or gene) gets modified,
This therapy does not inject mRNA.
I must be reading it wrong. It's using a harmless virus to modify mRNA. Please explain?
"Exons’ genetic information is transcribed into an intermediate molecule called messenger RNA (mRNA) that is used to guide protein production. Exons are translated and, much like with a puzzle, pieced together in the mRNA molecule.
…
Researchers at the Nationwide Children’s Hospital, in Ohio, developed an exon skipping therapy that uses a modified and harmless virus, called scAAV9.U7-ACCA, to deliver the genetic sequence of four molecules designed to force exon 2 skipping in the DMD gene’s mRNA. The one-time therapy is given directly into the bloodstream."
This therapy uses genetic material but not mRNA; however mRNA is the target. This therapy introduces DNA that encodes non-coding RNA. It is then this non-coding RNA that targets the DMD gene mRNA.
It looks like it doesn’t modify DNA, but it does modify what was just transcribed from the gene by removing an exon from the corresponding mRNA that came from the gene.
The source describes the 4 molecules the virus injects:
The definition of a gene from bleh wikipedia is: "A gene is a region of DNA that encodes function." And it goes on to say: "During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function."
For exon: "An exon is any part of a gene that will encode a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term exon refers to both the DNA sequence within a gene and to the corresponding sequence in RNA transcripts. In RNA splicing, introns are removed and exons are covalently joined to one another as part of generating the mature messenger RNA [mRNA]. Just as the entire set of genes for a species constitutes the genome, the entire set of exons constitutes the exome."
So, where I'm trying to go with this and what I'm trying to understand is, if muscular distrophy is a genetic disorder caused by a genetic mutation that causes a lack of a protein called dystrophin, and they're testing this gene therapy to fix a genetic mutation by modifying genes to produce more dystrophin, then how is that not modifying DNA? Is it because they're modifying the virus RNA to inject it's genes into a human, and so it's technically the virus that's modifying genes, hence DNA? From my understanding, an exon is a small section of a gene, and a gene is a small section of DNA.
Doing more research, is it because they're modifying mRNA to force it to make the dystrophin protein? mRNA is supposed to copy itself in the transcription process from DNA, and then use this copy to make proteins, or whatever it's function is. So, they're manipulating this DNA copy, the mRNA, to force it to produce the protein they want? How does it know when to stop? Isn't this what the mRNA COVID vaccines are doing? Or am I way off?
Sources:
https://en.m.wikipedia.org/wiki/Gene
https://en.m.wikipedia.org/wiki/Exon
https://www.technologynetworks.com/genomics/lists/what-are-the-key-differences-between-dna-and-rna-296719
From reading the source doc https://mdaconference.org/node/1150 , the scientists put 4 modified snRNA molecules into a virus to deliver into the cell.
From reading the main article, 11% of DMS sufferers have an issue with duplicate exon 2s. From basic biochemistry, when the mRNA with the extra exon 2 gets translated by the ribosome into dystrophin, the resulting dystrophin protein doesn’t work.
The 4 snRNA molecules per the main article prevent the extra exon 2s from being connected into the mRNA resulting in an mRNA that gets translated into a functioning dystrophin protein.
So there is no modification of the DNA, only the resulting mRNA that was transcribed from the DNA (or gene) gets modified,