Thread by @SimonWad

As promised, I'm uploading a thread of part of planned talk @_BSGCT Public Engagement Day @reneewatson77 @robynbell29 @virustinkerer @aarashsaleh @PopplewellGroup @morethanadodo @ralphdhector @ESGCT @DrNLK0 @PrenatalTherapy @ProtEngineer @CathyAbbottLab @jowinx @ValerieMarch

@GauchersA @DravetUK @Dr_RKarda @RickPrivolizzi @jantinaod @Bb_Margi @DrJo_Ng @CNSdrughunter

First up is a film from 2002. Halle Berry’s character, Jinx Johnson, is looking to have gene therapy courtesy of Simón Andreu’s character, Dr Alvarez. Any idea what the film is?

Any idea of the film? I'm leaving gaps so you can't see the answer.
.
.
.
.
.
.

Yup, James Bond’s 20th outing, “Die Another Day”. And it gets gene therapy way wrong, but there are a few useful things to learn here

i) Gene therapy, now, (e.g. inherited genetic disease) is almost never “gene replacement therapy”. Instead, working copies of the gene are delivered, in addition, to the body’s cells. It’s the genetic equivalent of a kidney transplant; the recipient’s old kidneys stay in.

ii) Gene therapy is a huge range of different technologies. In this film they are discussing gene therapy of bone marrow stem cells. This is “ex vivo” gene therapy – where a patient’s cells are isolated, the corrected gene is delivered, and the cells returned to the body.

“Ex vivo” gene therapy is the treatment of X-SCID, ADA-SCID, adrenoleukodystrophy and metachromatic leukodystrophy. It’s also being applied to sickle cell disease and thalassemia.

Gene therapy is also when the “vector” is injected directly into the patient to deliver genes directly into cells, tissues, organs. The injection might be into the brain, the eye, aerosolised for the lung, or injected intravenously.

iii) No, we don’t use the bone marrow of “strays and runaways” because the whole point of ex vivo gene therapy is that the patient gets their own -genetically corrected- cells back again. The patient is their own donor.

Ok, next up is a film where April Grace’s newscaster is interviewing Emma Thompson’s character, Dr Alice Crippen about an incredible new medical development. Any idea of the film?

Ok, maybe this clip will give you a clue

Yes, “I am Legend”. Dr Alice Crippen. What can we learn from Hollywood’s misinterpretations?

i) Here, gene therapy is being used to kill cancer, using a modified measles virus. For this gene therapy, the aim is to deliver genes that will kill cells and stimulate an immune response.

It’s almost the exact opposite of the type of gene therapy my colleagues and I do – gene therapy for inherited genetic disease, where we are trying to deliver working gene copies, and to avoid any immune response

ii) Dr Crippen’s virus not only cures cancer infects everyone and turning everyone into zombie-ish things. One thing for sure – whenever we (scientists) EVER change the genetic code of viruses (to make ‘em into vectors), we ALWAYS break them making them less effective viruses.

I guess a good comparison between a virus’ genetic material is with the most perfectly packed suitcase ever (watch on for this to be used in a film), everything lined up and fitting immaculately, like perfect Tetris.

In gene therapy we take the virus’ perfectly packed suitcase and try to fit in our basketball. It completely messes up the packing, and sometimes even messes up the suitcase.

Right, the penultimate film is James Franco’s Dr Will Rodman, telling potential investors in GenSys about…an incredible new medical development. But what is the film?

And here’s a clue. A bunch of non-human primates, one of whom looks like Andy Serkis (in between Gollum duties)

Yes! Return of the Planet of the Apes! So a few lessons to be learned from the Hollywood mess-up here.

i) If Hollywood is to be believed, gene therapy can distribute to all the cells in the body just by aerosol in the air. It CAN’T. In fact, it’s pretty tough even to infect your airways with a gene therapy vector.

This is a BIG difference between gene therapy vectors & viruses. If we breathe a virus in, it spreads through our airways. But a gene therapy vector IS NOT a virus – it can’t replicate, so every vector particle has one and only one shot at delivering its payload.

ii) The second major point is that in this film the gene therapy is transmitted to Caesar from his mother who receives the gene therapy. In other words, this is germline gene therapy – it changes the genetic makeup forever, being passed down generations

This is not how gene therapy works right now – changing the human germline is prohibited (and also technically difficult). So gene therapy only changes the body cells of the patient, but not the eggs in the ovaries or the sperm in the testes.

The 3rd point from the film is that gene therapy could make us super-intelligent. Codswallop. Intelligence involves thousands of genes, & in any case is very difficult to define (who’s smarter, Einstein, Picasso or David Beckham? I don’t see Picasso having his own fragrance line

And the final film is this. Jeremy Renner’s character Aaron Cross is being taught gene therapy by Dr Marta Shearing, played by Rachel Weisz.

Any idea?
.
.
.
.
.
.
A gold star for whoever guessed it as “The Bourne Legacy”. Aaron Cross is chemically-augmented, and wants permanent enhancement by taking gene therapy. Ok, they talk about using a virus, whereas they are virus-like particles called vectors.

But Dr Shearing wins a gold star too for her characterisation of gene therapy as a suitcase (you know, the one with the basketball). And she’s right – the challenge we STILL face with gene therapy is getting the gene to the right place, and in the right quantity.

And she’s also alludes to the need for a receptor “map”. Because we still have a lot to learn about the vectors we use. So while we are seeing more and more clinical success with gene therapy, there is lots of room for improvement.

Ok, that's all for now. Hopefully will upload more #scicomm #genetherapy material when I can reformat it. Stay safe and look after each other