7 Revolutionary Gene Therapy Breakthroughs in Healthcare


2017 was a year of pivotal gene therapy breakthroughs. Therapies involving cell-reprogramming received FDA-approval for treating B-cell leukemia and inherited vision and hearing loss. The research fraternity remarked this as an indomitable milestone since their decades of perseverance for the recognition of fundamental research was finally paying off. Almost organically, it rekindled investor activity, leading to better treatment designs for fatal conditions, including cancers.

This made for an intriguing watch amidst the stigmas of unmanageable mutations and failures associated with genomic medicine. A slight recall of not too long ago reveals frequent deaths plaguing gene therapy trials that brought investigation research to an uncanny still. Scientific literature of the 1990s alarmingly account the deviations of genetic research from its fundamental principles towards the methods developed to reduce gene manipulation failures. A record shift in the course of gene therapies came by in 2015 when novel technologies such as cell engineering and gene editing showed remarkable successes. Not surprisingly, the biotech and pharma industries caught the attention of this development and invested coercively on these developing biotechnologies.

The heroes of this story are gene-editing tools (including CRISPR) and genetic reprogramming of cells such as Kymriah and Yescarta. These gene therapy products, comprising CAR T-cells, established Gene Therapy as the viable alternative to traditional chemotherapy. This can be attributed not just to its high success rates but also to the long-standing scientific belief in the human innate immunity’s ability to fight cancer. Another distinctly appreciable victory for gene therapy was its application in curing sensory conditions, namely inherited vision loss and hearing loss, which got FDA-approval in the finishing week of 2017.

While we witness this vehemently positive shift in perspective, another hundred reports of experimental results await to see the light of the day. There are scientists exploring new cell reprogramming channels, better ways to visualize the DNA framework of disease-causing gene fragments, or creating pluripotent stem cells with specific regenerative capabilities. So, there are a plethora of scientific advances that need to be uncovered to understand how the further course of gene therapy will pan out. Without further ado,  here’s taking a look at the greatest gene therapy reports that have come in the last few weeks that have set the ball rolling for even bigger scientific breakthroughs.

#1 CAR-engineered Stem Cells that Treat HIV

Scientists at the at the Fred Hutchinson Cancer Research Center Lab at the University of California, Los Angeles and Washington have cultured and reprogrammed blood progenitor cells from the bone marrow to kill HIV-infected cells. This long-term gene therapy was reported in the PLOS Antigens journal recently, making it the first-of-its-kind application of hemopoietic stem progenitor cells (HSPCs) in CAR-mediated gene therapy. Onward from Kymriah’s success, scientists started probing other potential cellular constructs that can become successful candidates for incorporating novel therapeutic properties. Dr Scott G Kitchen said that reprogrammed HSPCs have a sustained effect, which is why they are favoured over peripheral T-cells with the protective CD4 receptor. The preliminary success of the hypothesis in cells was reported on primates and quite obviously, all we can do is wait for the same to be translated in humans.

#2 Engineered Natural Killer Cells against Hodgkin’s Lymphoma

As with cytotoxic T cells, scientists are curious about the capabilities of Natural Killer cells that express adaptive antibody-mediated cell-mediated cytotoxicities (ADCCs) against a vast spectrum of antigens. Natural Killer cells have a slighter chance of winning over T cells owing to their high activity in the close proximity of tumour cells. This is quite unlike T cells that induce necrotic changes in tumour cells through targeted molecules. Therefore, natural killer cells need a shorter time-frame to induce the same effect as CAR-mediated T cells. This potentially niche therapy is now the focal point of Fate Therapeutics’ current research for which the company has announced a collaboration with University of California, San Diego. So, it seems that gene therapies with re-engineered natural killer cells would figure in the category of targetted genomic treatments soon!

#3 Pectic Acid-based Corning Dissolvable Microcarriers for Cell Therapies

Cell Therapies require high throughput of redesigned cells that can be applied only when dissociated. The conventional form, i.e. cells as a solid immobilised matrix, disturbs the therapeutic system due to its contamination with undesired sugars and presents additional downstream processing challenges. Immobilized matrices of cells on bead-like microcarriers are important because they form the rudimentary structures on which Monoclonal Antibodies, proteins, cell signalling receptors or recognition markers are expressed. Cells growing on microcarriers become almost inseparable especially after they have expanded and developed to their full potential. Dissolvable microcarriers increase their efficacy by reducing toxicities, contaminations and increasing homogeneity so that the cells can be readily absorbed into the body and perform their designated therapeutic action.

#4 Development of Cell Expansion Systems for Gene-edited Blood and Immune Cells

Leukapheresis was, until this day, the process of choice for harvesting and growing T cells or B cells for delivering cell therapies into patients who need them. However, scaling their number for increasing the efficiency has been the immediate concern for R&D. High contamination rates accompany leukapheresis and then the underlying problem of manual-handling remained. This prompted Bioprocessing researcher, Andrew Fesnak, M.D., to incorporate large-scale, automated, closed cell expansion systems. These cell processing units have done away with manual intervention, risks of contamination and longer time periods using a well established ‘enrichment’ technology. Cell Saver and Sepax are the two new automated therapeutic cell expansion units by GE Healthcare, which closely compete with Cell Factory (R) by Thermo Fisher Scientific in terms of scalability and precision.

#5 Microsoft’s AI Tool for Fine Tuning CRISPR

CRISPR’s potential to change/cleave or improve gene expressions has made it a worldwide phenomenon and with the tech giant Microsoft’s interests growing immensely in healthcare, the path for CRISPR’s applicability only seems to get wider and brighter. Computational experts from Microsoft collaborated with multiple universities across the US and released Elevation – an Artificial Intelligence tool that alerts CRISPR about any undesired effects that may happen while it acts on genes. The research team that brought out this high accuracy prediction tool belong to distinguished academic institutions, including the Broad Institute of MIT and Harvard, Harvard Medical School and Massachusetts General Hospital. An ancillary tool named Azimuth accompanies Elevation, both of which can be accessed online as cloud-based end-to-end guide-design open source software.

#6 Exploring Zinc-Finger Nucleases against Hunter Syndrome

When CRISPR hit the headlines in mid-2015, there were immense conversations among biologists about the prospects of other genome editing modules. While some dismissed them off as inefficient, others just regained focus on the increased utility of TALENs and ZFNs. CRISPR may have crossed the barriers of investigation and entered into the clinical circuit, but that doesn’t take away the potential that Zinc Finger Nucleases and Transcriptor activator-like effector nucleases hold. Sangamo Therapeutics recently released a statement regarding its preliminary success in the ongoing Phase I/II clinical trial with a ZFN-mediated treatment for 9 patients with a genetic condition. 2018 is a crucial year for this investigational trial as a maximum of the patients are due for receiving the ZFN-mediated gene therapy. A positive clinical report in this clinical trial would mean that Zinc Finger Nucleases can be extensively used a parallel gene-editing tool alongside CRISPR in the future.

#7 Allogenic Stem Cells Based Gene Therapy for Crohn’s Disease

TiGenix and Takeda – both biotechnology companies in Belgium and Japan, respectively – have successfully displayed the treatment of perianal fistulas that are serious manifestations of Crohn’s disease. Being an autoimmune disease concerning the large and small intestine, Crohn’s patients require specialized diets and medicines. Cx601 – the gene therapy utilizing specialized adipose tissue cell constructs – was able to reduce host cell deduction and stimulate immunomodulatory effects of T cells. This unique expression of adipose-based stem cells enabled the generation of normal regulatory T cells that prevented the formation of perianal fistulas. Perianal fistulas present complex medical challenges and have devastating effects on patients, including death or severe gastrointestinal bleeding. Since perianal fistulas are commonly developed in patients with Crohn’s disease, this allogenic (from donors) genetic treatment is easily the best trial candidate for lowering risks associated with Crohn’s.

Genomic treatment seems to have attained a revolutionary status in the Biotech and Pharma arena, and the path currently steeps upward. From downstream processing to lab-on-a-chip devices, every single aspect of biotech product development has been touched by genomic engineering. This makes 2018 only getting more exciting with every passing day, so it’s best to set our eyes forward and only forward!

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About Author

Mahasweta is a Biotechnologist at heart with varied academic research experiences in Tissue Engineering, Medical Imaging Devices and Industrial Microbiology. She majored in Biomedical Engineering from Vellore Institute of Technology and has served as an editor for journal publications in Elsevier, Wolters Kluwer Health and Royal Society for Chemistry. She also writes for Company blogs, news articles and guest posts.

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