I need help with gene editing for a patient where just one G to A is causing the disease and taking a life. Can anybody suggest? All sequences are ready to be shared. Kindly guide.
Suhasini
A single G-to-A mutation causing a life-threatening disease can potentially be corrected using precise gene-editing techniques. The best approach depends on the specific gene, the affected tissue, and delivery method constraints. CRISPR/Cas9 systems have the potential to repair this… but I’m not 100% sure if we have a successful example of doing this in a person with such critical mutations. A generalized approach will be:
- Identify the exact gene and mutation location.
- Select the best gene-editing strategy based on cell type and delivery method.
- Use patient-derived iPSCs or animal models to test efficacy.
- Choose a safe and scalable delivery system (LNPs, AAV, or ex vivo approach).
You can connect with me directly through PM if you’d like to discuss about the gene or sequences.
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@Dr.Gaganjyot, For this patient, all sequencing has been done, infact both parents are heterozygous carriers and all sequences are avilable.Am just looking for step 4 now,The family stays at jaipur and we can visit physically if you are in India.I can provide all details.My mail id is suhasinibhatnagar@gmail.com. Kindly guide Sir. Regards Suhasini
Suhasini
Your account Chat or Direct Messaging is off so I reached out through your email. Share the details and we’ll see what we can do best to help out!
Oh am so sorry.my email id is suhasinibhatnagar@gmail.com.Please communicate here.Though am recieving replies from other people easily.Yet please write here. Regards Suhasini
Dr. Suhasini
We wrote to Dr. Navneet who is an expert with Gene editing and potential therapies, lets wait to hear it out from her. Keep me updated if Mr Gupta also receives a reply from her side. Let me again remind you that even if this is going to have any possibility of being used, it’s chances are still very narrow. But we keep the hope alive and get the best possible help through our network.
@ARGERINE .Yes Professor, am waiting for her reply.Shall update as I get something.
Another Loud thinking that I wish to discuss with you.Is it possible that we remove a portion of Madhav’s( patient from Jaipur) liver an then Transform one or two cells from the liver using a vector .Select 4 or 5 cells that have transformed an then we selectively remove these cells and selectively develop into a oragnoid.Transfer this later to the portion where Liver was removed, do you believe this should gradually regenerate. Just one aim that the Thymidine kinase that is not processing Uridine and that is causing toxicity in the patient and till a permanent solution is found, atleast we take care of the toxicity caused by Uridine substrate. Infact, I was asking Mr.rRamesh Gupta that we must try giving a small amount of enzyme( available from sigma as a poder) . The problem is that in this disease there is too much of uridine, that is not phosphort=ylated and the amounts build up gradually, causing toxicity in the blood.Understood that this enzyme functions inside mitochondria and primarily in liver but am aiming just one thing that Uridine that is not phosphorylated does not cause toxicity in the blood.May be now Uridine phosphate accumulates in blood and that is not removed,But I believe this could not cause toxicity.Am yet to understand if Uridine, phosphate will be taken back inside by cell wall and transformed, This I have to resaerch but mr.gupta is anxious to get his son married, atleast one child atleast he gets married. There are some 250 + families waiting fr me to help them an dI feel so restless.Can we do something? Asking for help but I don’t see much of an option for genetic diseases.Helpless that though we have the genome way back in 2003 but till date we have not been able to save a single life, except for sickle cell.This is bad. Regards Suhasini
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Suhasini
Science works at a different scale and pace from Analytical to Clinical Levels. Replanting the culture/ organoids may lead to development of aggressive forms of Cancer. Have you discussed the possibility of providing Thymidine Kinase exogenously to patient with a Doctor? These are the questions that you will need a basic answer.
- What’s the bioavailability?
- Dose?
- Kinetics of clearance?
- Toxicity of pure compound?
Thanks for just reading.As I mentioned these are just wild thoughts. I have yet not met an intelligent doctor who understands what I am saying.The medico here in India, in my opinion have managed to clear their studies on the baseline and somehow secure a job. My argument was that in a large number of cases you inject Insulin to a person so here why I cannot inject this enzyme? But no answers, they get confused.I wanted to do the research myself, but stuck again as the enzyme works in the mitochondrial membrane , pH must not be different but certain salts present may inhibit so again more research needed. Regards Suhasini
Suhasini
May be enlisting with a Hospital that does clinical Trials or Experimental Medication such as AIIMS where Researchers work along with Medical Practitioners might have a resolve. It is definitely not difficult to get an Analytical compound to convert to Medical Grade compound.
Can you check with any such Hospitals where you have links or if have a Research Center?
Yes, thanks for the lead.Am still looking for some guidance and leads.But not much is happening, so what if there are antibodies generated,I am convincing Mr.Gupta to take a chance and start atleast in a week’s time we will have an answer, but can understand, he is anxious that he may loose his son, so shut.
Regards Suhasini
Dr Suhasini
If you are working in India, you can check with AIIMS, New Delhi and they do a lot of clinical trials and experimental medicine. It might be time consuming though to take approval for a trial treatment at the administrative levels.
@Biographix, Thanks for the guidace, yes AIIMS was the first place, we tried approaching and getting guidance.But probably the person and the guidance we received, confused us still more.Its likely that the choice was wrong, can you suggest somebody more specific. Regards Suhasini
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Suhasini
Has there been any progress or positive information on this? Is there a possibility for providing any experimental medicines for such terminal patients
THANKS NAVNEET, I keep writing to Various people for help but absolutely nothing has happened till date.There are high amounts of deoxy uridine in the blood samples,and I was thinking what if I could inject the enzyme in the patients and atleast lower the deoxy uridine levels. But again am not sure, if this works.The enzyme works inside mitochondria so my doubt was will it work in Cytoplasm. There are no reports if it will work.As a random game,I even discussed with Mr.ramesh Gupta, the patients father about the plan. But I got stuck with-
- How do I dilute that powder as in what will be the solvent?
- How many units will be good?
- My plan was as there is no active assay to check for activity look at reduced levels of dUTP before and after injection and watch if the enzyme works.But Mr.Gupta was a bit apprehensive.People told him that this act may induce antibodies and that may further complicate.He got so apprehensive that he did not even order the Uridinylase powder available from Sigma. Infact, the Sigma people said they need to import from USA so they will need a letter from the head of the treating hospital to import .So all this just complicated a small stuff too.I tried to explain to people but felt that maybe I am not the right person. Nobody except Dr. Gaganjot of The Scientist Solutions supports. Had a very simple plan to help but I was born at a wrong place and at a wrong time.Now, if you have something in mind, please discuss, I want to help these people.
Sorry not Gurpreet but Dr.Gaganjot Singh. Misspelled,Very bad at remembering names. Regards Suhasini
Suhasini
I came across these today and probably worth reaching out regarding the MNGIE
Thanks.Yes I wrote to this professor earlier too. A renowned Scientist who does not have time to reply. Regards Suhasini
Ironically, Science has become confined to only publications and show casing your results but not about helping out.