This treatment does not use CRISPR. It involves the hollowed out and repurposed lentivirus (similar in kind to HIV)[1]. The virus keeps it's own viral 'insert-into-DNA' machinery, but is stripped of its replication machinery as well as the code for its physical shell. The insert-into-DNA machinery is further hijacked so it can insert nothing but the DNA that encodes for the new mutated hemoglobin (HBB [T87Q][2]) that, when the patient's cell reads that new DNA will produce a new version of the protein. That insertion machinery with its new payload is loaded into a viral shell in a lab somewhere (again, its replication machinery and the code for new shells has been gutted).
When this new virus is given to the patients it does indeed infect the patients' cells. It uses its viral machinery to insert itself into the genome of the patient, more or less randomly - and that is not ideal. CRISPR systems are much newer and are being worked on right now, but the technologies you see in use in this article predate CRISPR. CRISPR will only speed up what was here a monumental (and slightly more risky) effort.
Regardless of how the code gets inserted into the genome (lentiviral in this case, CRISPR likely in future therapies), the instruction set to produce the new protein is not only capable of doing the job of the broken hemoglobin, but actually enables the broken hemoglobin to regain some of its function, likely coming very close to actually curing the patient.
In computer terms, someone with sickle-cell disease has a typo in the source code that leads to a buffer overflow error in the oxygen transport module. We found stuxnet can inject live code into a running OS, so we stripped it of its payload, it's ability to replicate but kept its injection capabilities and gave it our hot-fix as its payload. Our patch will be injected into billions of running nodes, inserting a ~500 line patch randomly into the each node's memory stack (yes, that's scary - but if a few of the nodes (cells) go down, it's not a horrible problem, and the current price of doing the patch at all... CRISPR can help here in future versions). That new code provides not only an alternative oxygen transport package, but this new package, so long as its running on >20% of the nodes, actually forces the original code's memory to periodically flush, thus de facto correcting the original typo's overflow bug - allowing both the new package and the old (kinda bug-fixed) package to both now be useful oxygen transport code. No more bug = cure.
The patients had a code regression, and we're applying not just a 1.0 fix, but a very real 1.1 patch on the human hemoglobin instruction set (randomly, into live code, on millions if not billions of cells, using modified HIV technology).
Thank you for this brilliant and detailed explanation showing the differences between CRIPR and the virus method! I haven't seen anyone explain the concept of viruses in the language of buffer overflows! Delightful.
The lentivirus has a number of capabilities - insert into cell, insert into DNA, replicate payload, build capsid, encapsidate payload, escape cell. In this particular case the lentivirus was used both for it's 'insert into cell' as well as its 'insert into dna' capabilities - with all others being stripped.
CRISPR (more specifically, Cas9) is another protein machine that locates particular DNA sequences [1]. It can help take over from the lentivirus with respect to the 'insert into dna' capability. But you're right, we still have no better way to get it into the cell than to use a (lenti)-virus's own 'insert-into-cell' machinery. So a lentivirus might be used along with CRIPSR in order to just get CRISPR machinery into the cell.
This is further muddled by the fact that sometimes you actually want the dna that encodes for your CRISPR system to itself be inserted into the genome, and in that case you might keep both the lentivirus's 'insert-into-dna' machinery AND the CRISPR's own 'insert-into-dna' capability.
At the end of the day, lentivirus's capability to insert into DNA is not predictable, and therefore a bit dangerous (if it inserts its payload in the middle of an oncogene in a predisposed cell you could get cancer). CRISPR is a device which promises to bring specificity to the command, making it 'insert-into-dna-AT'. And in that way it could replace the job of lentivirus in the above gene editing technique.
When this new virus is given to the patients it does indeed infect the patients' cells. It uses its viral machinery to insert itself into the genome of the patient, more or less randomly - and that is not ideal. CRISPR systems are much newer and are being worked on right now, but the technologies you see in use in this article predate CRISPR. CRISPR will only speed up what was here a monumental (and slightly more risky) effort.
Regardless of how the code gets inserted into the genome (lentiviral in this case, CRISPR likely in future therapies), the instruction set to produce the new protein is not only capable of doing the job of the broken hemoglobin, but actually enables the broken hemoglobin to regain some of its function, likely coming very close to actually curing the patient.
In computer terms, someone with sickle-cell disease has a typo in the source code that leads to a buffer overflow error in the oxygen transport module. We found stuxnet can inject live code into a running OS, so we stripped it of its payload, it's ability to replicate but kept its injection capabilities and gave it our hot-fix as its payload. Our patch will be injected into billions of running nodes, inserting a ~500 line patch randomly into the each node's memory stack (yes, that's scary - but if a few of the nodes (cells) go down, it's not a horrible problem, and the current price of doing the patch at all... CRISPR can help here in future versions). That new code provides not only an alternative oxygen transport package, but this new package, so long as its running on >20% of the nodes, actually forces the original code's memory to periodically flush, thus de facto correcting the original typo's overflow bug - allowing both the new package and the old (kinda bug-fixed) package to both now be useful oxygen transport code. No more bug = cure.
The patients had a code regression, and we're applying not just a 1.0 fix, but a very real 1.1 patch on the human hemoglobin instruction set (randomly, into live code, on millions if not billions of cells, using modified HIV technology).
Diagram of the patch's entire injected instruction set (8.5kb): https://www.ncbi.nlm.nih.gov/core/lw/2.0/html/tileshop_pmc/t...
[1] Lentivirus: https://en.wikipedia.org/wiki/Lentivirus
[2] The 'updated' hemoglobin: https://serotiny.bio/notes/proteins/hbb/