4 ms·

Could you elaborate for a bio know-nothing like me? It comes across as a very dismissive comment when one of the scientists is quoted saying: "You would inject

by dstick 8y ago

Could you elaborate for a bio know-nothing like me? It comes across as a very dismissive comment when one of the scientists is quoted saying: "You would inject this virus into a person's eye and, a couple months later, they'd be seeing something," Seems like a pretty big deal to me?

snovv_crash 8y ago
It's the bio-equivalent of saying "By restoring a single file, the webcam started working again!" In this case the vector for restoring the knocked out gene happens to be a virus.
- pmart123 8y ago
  Nice analogy.
- squarefoot 8y ago
  Following the same analogy, could we say that researches knew what exact file was missing and happened to have that same file at hand? In other words, making this applicable to blind humans with different kinds of blindness would be a whole different story?
  - snovv_crash 8y ago
    Yes. They removed the file, then put it back. The study is about proving the insertion vector works for whatever treatment needs to be done in the future, not about being able to cure blindness.
- omidkarkouti 8y ago
  Incorrect. Please see my response to gus_massa above.
  - snovv_crash 8y ago
    No, this is correct. They've identified 2 known corrupted 'files', and by restoring them from 'backup' they were able to restore functionality. What is cool/notable is that the restore method worked on a running device, and they didn't even need to 'reboot' for the fix to take effect.
gus_massa 8y ago
This are not normal mice that gone blind. These are special mice that have one of they gene broken. (The same gene in all the mice in the experiment.) So it is "easy" to fix their problem by giving them a new working copy of the defective gene. It's a nice result, but now the interesting question is if this can be generalized to people that doesn't have that a more diverse type of problems. See also https://en.wikipedia.org/wiki/Synthetic_rescue https://en.wikipedia.org/wiki/Synthetic_rescue https://en.wikipedia.org/wiki/Gene_knockout https://en.wikipedia.org/wiki/Gene_knockout
- omidkarkouti 8y ago
  I'd like to provide you with some more background because you are conflating this research with a different type of study and incorrectly interpreting its impact. For background, I have inherited retinal disease in my family, am the founder of a gene therapy company that is working on genetic blindness, and have met John Flannery a few times. This is not a simple 1) knockout gene in mouse, 2) put same gene back in study, like has been done many times before. The model system here, the rd1 mouse, is not a "knockout mouse" per se. It is a strain of visually impaired lab mouse that was identified in the 1920s before knockout mouse technology was available. These mice have mutations in the PDE6B gene (due to a virus insertion) and the Gpr179 gene (which was identified much later). Rd1 mice have severe early onset blindness caused by the death of cells that allow normal eyes to perceive light - photoreceptors. In these mice, the rod photoreceptors die first, then the cone photoreceptors follow, and this all happens pretty quickly. In this study, researchers are introducing a different gene (green cone opsin) into second-order cells that do not normally perceive light (retinal ganglion cells or bipolar cells). This approach gives retinal ganglion cells/bipolar cells the new ability to perceive light. Importantly, these cells survive in patients that are blind because of photoreceptor death, so this approach can be generalized. Scientists have been trying this for a while and there have been a number of limitations due to the performance of the introduced genes (opsins). There are clinical trials planned and ongoing in optogenetics, but those include things like light filters/amplifiers, and also often some form of implant. It is not yet clear the quality / resolution of vision that people could regain. A very good outcome with the technology described would be providing monochrome vision of useful resolution to patients who currently cannot perceive light at all. There are likely many subtleties I haven't considered or don't know about. Nevertheless, this is significant progress with an approach that is in theory applicable to very advanced cases of over 270 genetic diseases that cause blindness.
omidkarkouti 8y ago
You're right. If it works, this is a really big deal for many people who have gone blind from photoreceptor diseases like retinitis pigmentosa.

by dstick 8y ago

snovv_crash 8y ago

It's the bio-equivalent of saying "By restoring a single file, the webcam started working again!" In this case the vector for restoring the knocked out gene happens to be a virus.

pmart123 8y ago
Nice analogy.
squarefoot 8y ago
Following the same analogy, could we say that researches knew what exact file was missing and happened to have that same file at hand? In other words, making this applicable to blind humans with different kinds of blindness would be a whole different story?
- snovv_crash 8y ago
  Yes. They removed the file, then put it back. The study is about proving the insertion vector works for whatever treatment needs to be done in the future, not about being able to cure blindness.
omidkarkouti 8y ago
Incorrect. Please see my response to gus_massa above.
- snovv_crash 8y ago
  No, this is correct. They've identified 2 known corrupted 'files', and by restoring them from 'backup' they were able to restore functionality. What is cool/notable is that the restore method worked on a running device, and they didn't even need to 'reboot' for the fix to take effect.

gus_massa 8y ago

This are not normal mice that gone blind. These are special mice that have one of they gene broken. (The same gene in all the mice in the experiment.) So it is "easy" to fix their problem by giving them a new working copy of the defective gene. It's a nice result, but now the interesting question is if this can be generalized to people that doesn't have that a more diverse type of problems. See also https://en.wikipedia.org/wiki/Synthetic_rescue https://en.wikipedia.org/wiki/Synthetic_rescue https://en.wikipedia.org/wiki/Gene_knockout https://en.wikipedia.org/wiki/Gene_knockout

omidkarkouti 8y ago
I'd like to provide you with some more background because you are conflating this research with a different type of study and incorrectly interpreting its impact. For background, I have inherited retinal disease in my family, am the founder of a gene therapy company that is working on genetic blindness, and have met John Flannery a few times. This is not a simple 1) knockout gene in mouse, 2) put same gene back in study, like has been done many times before. The model system here, the rd1 mouse, is not a "knockout mouse" per se. It is a strain of visually impaired lab mouse that was identified in the 1920s before knockout mouse technology was available. These mice have mutations in the PDE6B gene (due to a virus insertion) and the Gpr179 gene (which was identified much later). Rd1 mice have severe early onset blindness caused by the death of cells that allow normal eyes to perceive light - photoreceptors. In these mice, the rod photoreceptors die first, then the cone photoreceptors follow, and this all happens pretty quickly. In this study, researchers are introducing a different gene (green cone opsin) into second-order cells that do not normally perceive light (retinal ganglion cells or bipolar cells). This approach gives retinal ganglion cells/bipolar cells the new ability to perceive light. Importantly, these cells survive in patients that are blind because of photoreceptor death, so this approach can be generalized. Scientists have been trying this for a while and there have been a number of limitations due to the performance of the introduced genes (opsins). There are clinical trials planned and ongoing in optogenetics, but those include things like light filters/amplifiers, and also often some form of implant. It is not yet clear the quality / resolution of vision that people could regain. A very good outcome with the technology described would be providing monochrome vision of useful resolution to patients who currently cannot perceive light at all. There are likely many subtleties I haven't considered or don't know about. Nevertheless, this is significant progress with an approach that is in theory applicable to very advanced cases of over 270 genetic diseases that cause blindness.

omidkarkouti 8y ago

You're right. If it works, this is a really big deal for many people who have gone blind from photoreceptor diseases like retinitis pigmentosa.