Mysterious Radio

My special guest is Eben Kirksey who’s here to discuss his book about the fast growing world-wide interest in manipulating human DNA. Get his book The Mutant Project: Inside the Global Race to Genetically Modify Humans on Amazon.

Longlisted for the Baillie Gifford Prize 2021 An anthropologist visits the frontiers of genetics, medicine, and technology to ask: whose values are guiding gene-editing experiments, and what are the implications for humanity? At a conference in Hong Kong in November 2018, Dr. Jiankui He announced that he had created the first genetically modified babies—twin girls named Lulu and Nana—sending shockwaves around the world. A year later, a Chinese court sentenced Dr. He to three years in prison for “illegal medical practice.” As scientists elsewhere start to catch up with China’s vast genetic research programme, gene editing is fuelling an innovation economy that threatens to widen racial and economic inequality. Fundamental questions about science, health, and social justice are at stake. Who gets access to gene-editing technologies? As countries loosen regulations around the globe, can we shape research agendas to promote an ethical and fair society? Professor Eben Kirksey takes us on a groundbreaking journey to meet the key scientists, lobbyists, and entrepreneurs who are bringing cutting-edge genetic modification tools like CRISPR to your local clinic. He also ventures beyond the scientific echo chamber, talking to doctors, hackers, chronically ill patients, disabled scholars, and activists and who have alternative visions of a genetically modified future for humanity. The Mutant Project empowers us to ask the right questions, uncover the truth, and navigate this new era of scientific enquiry.

Gene therapy is a medical field which focuses on the genetic modification of cells to produce a therapeutic effect[1] or the treatment of disease by repairing or reconstructing defective genetic material.[2] The first attempt at modifying human DNA was performed in 1980, by Martin Cline, but the first successful nuclear gene transfer in humans, approved by the National Institutes of Health, was performed in May 1989.[3] The first therapeutic use of gene transfer as well as the first direct insertion of human DNA into the nuclear genome was performed by French Anderson in a trial starting in September 1990. It is thought to be able to cure many genetic disorders or treat them over time.

Between 1989 and December 2018, over 2,900 clinical trials were conducted, with more than half of them in phase I.[4] In 2003, Gendicine became the first gene therapy to receive regulatory approval. Since that time, further gene therapy drugs were approved, such as Glybera (2012), Strimvelis (2016), Kymriah (2017), Luxturna (2017), Onpattro (2018), Zolgensma (2019), Abecma (2021), Adstiladrin, Roctavian and Hemgenix (all 2022). Most of these approaches utilize adeno-associated viruses (AAVs) and lentiviruses for performing gene insertions, in vivo and ex vivo, respectively. AAVs are characterized by stabilizing the viral capsid, lower immunogenicity, ability to transduce both dividing and nondividing cells, the potential to integrate site specifically and to achieve long-term expression in the in-vivo treatment. (Gorell et al. 2014) ASO / siRNA approaches such as those conducted by Alnylam and Ionis Pharmaceuticals require non-viral delivery systems, and utilize alternative mechanisms for trafficking to liver cells by way of GalNActransporters.

The concept of gene therapy is to fix a genetic problem at its source. If, for instance, a mutation in a certain gene causes the production of a dysfunctional protein resulting (usually recessively) in an inherited disease, gene therapy could be used to deliver a copy of this gene that does not contain the deleterious mutation and thereby produces a functional protein. This strategy is referred to as gene replacement therapy and is employed to treat inherited retinal diseases.[5][6]

While the concept of gene replacement therapy is mostly suitable for recessive diseases, novel strategies have been suggested that are capable of also treating conditions with a dominant pattern of inheritance.

• The introduction of CRISPR gene editing has opened new doors for its application and utilization in gene therapy, as instead of pure replacement of a gene, it enables correction of the particular genetic defect.[7] Solutions to medical hurdles, such as the eradication of latent human immunodeficiency virus (HIV) reservoirs and correction of the mutation that causes sickle cell disease, may be available as a therapeutic option in the future.[8][9][10]
• Prosthetic gene therapy aims to enable cells of the body to take over functions they physiologically do not carry out. One example is the so-called vision restoration gene therapy, that aims to restore vision in patients with end-stage retinal diseases.[11][12] In end-stage retinal diseases, the photoreceptors, as the primary light sensitive cells of the retina are irreversibly lost. By the means of prosthetic gene therapy light sensitive proteins are delivered into the remaining cells of the retina, to render them light sensitive and thereby enable them to signal visual information towards the brain.

Not all medical procedures that introduce alterations to a patient’s genetic makeup can be considered gene therapy. Bone marrow transplantationand organ transplants in general have been found to introduce foreign DNA into patients.[13]

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