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Does anyone know: what are the failure rates like for the gene editing technology being used for this? Thinking like a software engineer, are there transpositio

by sjbase 9y ago

Does anyone know: what are the failure rates like for the gene editing technology being used for this? Thinking like a software engineer, are there transposition errors (GATC --> GTAC) , atomicity issues (GATC --> GA)? Mutations afterward?

jfarlow 9y ago
In this particular case the therapy is being applied to cells that have been extracted from a patient. That allows a reasonable error rate where errors can be filtered out, and success verified before the cells are reimplanted. This is a strategically nice intermediate before having to run a therapy on a living organism. The technology in use here is not quite the same kind of 'DNA editing' as is found with tools like CRISPR, but rather a much more therapeutically mature (if technologically blunt) form of viral 'insertion of a block of code'. With respect to actual code fidelity, errors in DNA come from a number of different sources. Every time DNA is copied (a cell divides) there is an inherent fidelity rate of the copy (on the order of a single mistake per billion writes). The payload here is on the order of a few thousand base pairs so copies should have a very high fidelity. In this case a viral protein is 'inserting' its DNA randomly into the genome of the target cells. Imagine inserting a library of code randomly into a codebase. Certainly not ideal, and an issue that CRISPR technologies promise to help improve. However, given that the therapy is only being applied to immune cells that are only running the 'immune' section of the human codebase, and no progeny of those cells will ever have to become a brain or skin or run any of the other programs, the chance that the inserted DNA disrupts the 'immunological' code in the codebase is relatively small. And if there is disruption to some cells' genomes those cells could be screened out if they really distort something they should not. With respect to DNA generally, common errors arise from undesirable but common chemical modifications to the code itself. The DNA can become damaged (by reactive oxygen, UV light, and through other chemical reactions), and while there are significant systems to repair that damage, oftentimes since there is only a single backup (DNA is 'double-stranded'), it's often impossible for that machinery to determine whether the error is on strand1 or strand2, so 50/50 chance of 'repairing' into the error.

by sjbase 9y ago

jfarlow 9y ago

In this particular case the therapy is being applied to cells that have been extracted from a patient. That allows a reasonable error rate where errors can be filtered out, and success verified before the cells are reimplanted. This is a strategically nice intermediate before having to run a therapy on a living organism. The technology in use here is not quite the same kind of 'DNA editing' as is found with tools like CRISPR, but rather a much more therapeutically mature (if technologically blunt) form of viral 'insertion of a block of code'. With respect to actual code fidelity, errors in DNA come from a number of different sources. Every time DNA is copied (a cell divides) there is an inherent fidelity rate of the copy (on the order of a single mistake per billion writes). The payload here is on the order of a few thousand base pairs so copies should have a very high fidelity. In this case a viral protein is 'inserting' its DNA randomly into the genome of the target cells. Imagine inserting a library of code randomly into a codebase. Certainly not ideal, and an issue that CRISPR technologies promise to help improve. However, given that the therapy is only being applied to immune cells that are only running the 'immune' section of the human codebase, and no progeny of those cells will ever have to become a brain or skin or run any of the other programs, the chance that the inserted DNA disrupts the 'immunological' code in the codebase is relatively small. And if there is disruption to some cells' genomes those cells could be screened out if they really distort something they should not. With respect to DNA generally, common errors arise from undesirable but common chemical modifications to the code itself. The DNA can become damaged (by reactive oxygen, UV light, and through other chemical reactions), and while there are significant systems to repair that damage, oftentimes since there is only a single backup (DNA is 'double-stranded'), it's often impossible for that machinery to determine whether the error is on strand1 or strand2, so 50/50 chance of 'repairing' into the error.