Patience for hMSCs in COVID-19: We Must Crawl Before We Run

Crawl-Walk-Run

“If you can’t fly then run, if you can’t run then walk, if you can’t walk then crawl, but whatever you do you have to keep moving forward.” ― Martin Luther King Jr. [1]

The metaphor of “Crawl-Walk-Run” (or its converse) has been stretched in infinite directions since MLK’s encouraging words were spoken in his speeches to colleges. Today, a global pandemic from SARS-CoV-2 threatens millions of lives in every country on Earth through its direct [2] and indirect [3] impacts. Facing COVID-19, our species is caught in a vulnerable and disoriented state, not unlike that of a human infant.  Can we apply this metaphor even further–toward the state of clinical readiness for regenerative cell therapies for COVID-19 damaged lungs?

Although efforts to use human mesenchymal stromal/stem cells (hMSCs) vs. the end stage of COVID-19 (Acute Respiratory Syndrome; ARDS) are probably well beyond a neonate’s “Fourth Trimester,” [4] most would agree that this unique approach is still akin to the “Crawl” stage of childhood motor development.  Like infant milestones, each new glimmer of hope from a promising new treatment modality like hMSCs for COVID-19/ARDS will be eagerly welcomed. Yet, despite our best efforts and hopes to see the child swiftly run, there will be fumbles along the way, and this child will need protection from both itself and hazards in his or her path. Realistically, if past medical technology advances are any guide, we can likely look forward to no “running start” for MSCs used against ARDS. Patience is part of the “JD” for any parent, and it’s a prerequisite for cell therapy developers, too. [5] [6]

Crawling

After months of near-complete helplessness, the crawling human infant has already learned to roll over, sit up, grab objects, and reach for the hearts of her adoring parents. Children at this stage understand basic cause and effect, how to say a few words; just a little extra effort can make them get where they want to go. They become wired for motion, motivated to get closer to the objects of their wishes—whether it is a chew toy, the kitty cat, or a nearby hardwood stairwell. They can summon your attention, too–by cooing or laughing sweetly, or abrupt screaming, or even by sudden silence. The cell therapy RegenMed community wants the “baby” of MSCs for COVID-19/ARDS to succeed, by coaxing her to confidently explore and understand the patterns of the big world that her siblings effortlessly navigate; yet also, the parent guards her every move, because it’s a very long tumble down the stairs.

Today, we’ve noticed a stirring of sudden clinical development launches with MSCs or MSC extracellular vesicles since January in response to COVID-19. Clinicaltrials.gov lists at least 13 such interventional trials at the present date; [7] Cade Hildreth of BioInformant.com has been following developments in this arena, and tracking announcements of new MSC-related IND filings or trials even before listing on clinicaltrials.gov (HERE: link to summary post from 2-April-2020). [8] Among these are Pluristem’s PLX cells used in three COVID-19 patients under Israel’s compassionate use guidelines, [9] Mesoblast’s plans to employ its remestemcel-L MSC product against COVID-19/ARDS, [10] and Athersys MultiStem® bone marrow-derived stem cells recognition by BARDA as a “highly relevant” therapeutic for ARDS and COVID-19; [11] in relation to ARDS, Athersys reported improvements in patient quality of life at 28-day and 1 year timepoints, including metrics of ICU-free days, ventilator-free days, and reduced mortality. In addition, Hildreth reported (9-April, HERE) FDA approval for a Phase II trial to evaluate safety and efficacy of Hope Biosciences’ autologous, adipose-derived MSCs as a prophylactic against COVID-19’s cytokine storm effects seen in some patients. [12] Other MSC-related activity is being noted with Aspire Health Science’s umbilical cord MSCs, and Citius Pharma’s and Cynata Therapeutics’ iPSC-derived MSCs. [13]

Interestingly, seven COVID-19 pneumonia patients treated with IV-injected MSCs at Beijing’s YouAn Hospital appeared to significantly and rapidly improve in their symptoms. An additional 24 are being tested with reportedly positive outcomes. [14] [15]  Although this was a small trial under non-optimized study conditions, such results appear encouraging enough to inspire further study. These COVID-19 related studies are built on the foundation of a prior work performed by UCSF’s Professor Dr. Michael Matthay, MD and colleagues to treat generalized infection-induced ARDS. [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] Such earlier work with MSCs in preclinical and human ex vivo models provided a highly compelling rationale for study; however, related Phase II studies did not yet show signs of efficacy. The MSC “secretome” may offer a parallel, if not a less fully-mature therapeutic approach than use of whole MSCs (see our blog on this topic, HERE). [27] Although preclinical evidence [28] [29] [30] to support therapeutic MSC exosomes and extracellular vesicles (EVs) is fascinating—and beginning to build momentum for new COVID-19/ARDS related trials—[31] [32] definitive results from these will take many more months.

To the casual eye, this pre-ambulatory “infant” state of trial and error in therapeutic options for COVID-19/ARDS can seem static, or perhaps even haphazard or unsophisticated.  However, as any parent or pediatrician will tell you, a crawling infant’s brain flashes with intense and brilliant learning that becomes hard-wired into her lifelong models of reality. Similarly, our present state of “crawling” in this industry gives us a chance for retrospection into old data embedded in different patient cohorts or samples, or perhaps to look for overlooked patterns via principal components analyses of missing “omics” biomarkers. [33] [34] These and other learning opportunities will provide investigators with the best set of tools to design new studies that will empower our infant with the awesome responsibility of autonomous “walking.”

Walking

Evolution of human bipedal motion about four million years ago is a mystery. Perhaps it came about during natural selection of our hominid ancestors who waded through an aquatic environment, [35] or to spot predators while hiding in fields of tall grass away from the safe canopy of the forest. [36]  Regardless, for we stargazing humans, walking does not happen as easily as for many other mammals, who are perfectly content to ruminate among the herds for their survival.

Prior to walking, a human child learns to stand with assistance from a hand or the side of a crib, or a table.  Similarly, our fledgling institutions and biotech companies that are specialized to clinically develop MSC-based pipelines for COVID-19/ARDS will need standard sets of familiar and non-hazardous “assists” and tools to reach a standing position. These include cGMP media and cell systems, donor-qualified Working Cell Banks (WCBs) on file with the FDA, and scalable approaches that inform every step: from small kits for starting research, to bioreactors that are capable of supplying hundreds to thousands of doses or more. [37] [38] [39]

At around one year of age, the child hazards a step or two, “falling” by accident, yet then catching himself with their other foot. Parents or elders are quick to notice these first “missteps,” and then reinforce this exhilarating sensation with praise and applause, and a hand to guide him. Like a toddler learning to walk, the science of MSCs to treat COVID-19/ARDS will seem hesitating at first, and will need a helping hand from lots of experienced (and bigger) advocates.  Walking involves the risk of falling, too, and the toddler’s parents must weigh that ever-precarious balance between over-protective nurture and wild nature.  For MSCs in RegenMed therapies, there have been many “falls”— instant conversions of exuberant mirth into tearful face-plants, bruised craniums, and skinned knees.  And yet… our “toddler” is still very much alive and kicking, and some say, soon to meet its moment of destiny à la CAR-T’s inflection point of 2013. [40]

What will the “first steps” of an MSC-based therapy against COVD-19/ARDS look like?  Just as walking is a natural characteristic of most humans, MSCs are a natural feature of the human response to tissue injury, capable of homing towards a lesion and secreting paracrine factors to recruit multiple cell types that are essential for healing. [41]  It is therefore not a matter of “if,” but “when.”  Let’s set this key inflection point at when we see compelling phase II data, suggestive of both safety and efficacy in human patients for an ARDS condition.

According to Hay et al’s 2014 survey, for the average respiratory indication drug, the average Likelihood of Approval (LOA) from beginning of Phase I to FDA Approval is ~11%; for infectious diseases this estimate is ~17%. Nevertheless, the chance of successfully proceeding through Phase III studies after a positive Phase II is 63% and 65%, respectively. [42] Even if these estimates improve with outstanding efficacy due to a unique MSC product and drug process, the large amount of capital and resources needed to run multi-center, Phase III trials is likely remain a barrier for MSC-ARDS developers. This barrier will be overcome when companies and institutions show that they can be masters of their own fate with regard to candidate discovery, IND-enabling preclinical study, and early human trials. Like young toddlers, they will need to prove that they can negotiate their own surroundings safely, before given the resources to come and go freely. For diseases with short windows of time to gather endpoints (e.g., acute infectious diseases), the amount of time from IND filing to the end of Phase II can take at least a year; this assumes that translational centers are lined up with dozens of qualified patients, supplied with robust logistics to manage a steady throughput of consistently manufactured cell doses.  Like children with caring parents, clinical developers who are committed to quality of their cell product from the very inception will have a less difficult path ahead. [37]

Running

After a few bumps and bruises, one day you will see your child run, probably in a wide-open space like a park, a backyard, or a playground. Her motivation…To keep up with the other runners her own age, or to evade a parent who wants to bring her home for lunch and a nap. For the human species, we began running to escape predators, to track and pursue prey, and perhaps, just because it is fun.

With MSCs deployed against COVID-19/ARDS, it’s possible (even hopeful) that the COVID-19 pandemic will be a fading memory by the time this field of study is ready to truly “run.” Even so, severe COVID-19 causes a generalized set of pathologies that may include ARDS, [43] a broader condition may be addressable by the same MSCs that were enlisted in the mobilization for battle with the SARS-CoV-2 pathogen. Thus, although there may emerge a very competitive “playground” for MSCs in the specialized COVID-19 space, there will be many other examples and indications where MSCs could be beneficially deployed in acute syndromes of the lung. For example, nefarious actors could unleash chemical-biological-radiological-nuclear (CBRN) agents, for which a large national stockpile of MSCs could be drawn from in case of emergency. [44] For more mundane (but still very urgent) application, ARDS affected 200,000 people each year in the USA before COVID-19, where 40% died from it. [45] Whether from flu, coronavirus, “pathogen X,” or chemical injury, ARDS remains a dire unmet medical need with multiple sub-phenotypes to assist in different treatment options or clinical trial patient stratification. [46]

What does an MSC therapeutic space against COVID-19 look like in its “Run” stage? Running will occur when there is at least one FDA-approved drug based on MSCs (or MSC-EVs) approved for the market and in production. This requires a large-scale ramp-up in cell biomanufacturing capacity above present day levels. We have blogged on this very topic recently (HERE). [47] This will be readily achievable with a modest increase in capital investment to validate MSC bioreactor runs at cell volumes >10-fold larger than 50L, i.e., 500L+.

Yet, after supply becomes more plentiful and COGS is brought down to a few tens of dollars per dose via economies of scale, what’s next?  It is difficult to predict the kinds of breakthroughs that will offer “next-gen” therapeutic approaches that will improve upon the prospective standard of care based on MSCs to treat COVID-19 and/or ARDS.  Given that MSCs can be genetically modified for enhanced biofunction, [48] various investigators have shown that this cell class can serve as a “chassis” for highly sophisticated gene circuitry, assembled from a catalog of standardized “synbio” parts to create controllable therapeutic “devices.” One notable example from 2018 is from Dr. Martin Fussenegger’s group at ETH Zurich, where MSCs were equipped with T-cell like functions. [49] Another recent example, published in a non-peer-reviewed study from Stanford U., developed a CRISPR-based system to disrupt COVID-19. [50]  Investigators have begun to evaluate loading targeted exosomes/EVs with recombinant AAV, [51] RNAi, [52], or CRISPR/Cas, [53] invoking intriguing possibilities for “MSC 2.0” to assist in biomanufacturing of such delivery systems.

Conclusion

Q: “Which creature has one voice and yet becomes four-footed, and two-footed, and three-footed

– The Sphinx. ~500 BCE

A: “The humans – who crawl on all fours as a baby, then walk on two feet as an adult, and then use a walking stick in old age.”

– Oedipus

The archetype of our ascent into a state of bipedal motion from crawling is an ancient one, and a source of endless myth and mystery. It even underlies the journey of MSCs as a technology to target the terrible fate of patients with end-stage COVID-19/ARDS.  Just as we fervently hope these patients to get well again out of their own supine state–to restore their lives, and renew the joy of their first steps from long ago–we as enablers and developers strive to be ready to give them a hand, with the best tools that regenerative medicine can offer.

 

References

  1. Jr., M.K. If you can’t run then walk – Martin Luther King. YouTube; Available from: https://www.youtube.com/watch?v=MFOFs0iAwDg&feature=youtu.be&t=120.
  2. Dong, E., H. Du, and L. Gardner, An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis, 2020. 10.1016/S1473-3099(20)30120-1
  3. Jorgensen, M.B., et al., Alcohol consumption and labour market participation: a prospective cohort study of transitions between work, unemployment, sickness absence, and social benefits. Eur J Epidemiol, 2019. 34(4): p. 397-407. 10.1007/s10654-018-0476-7
  4. NPR and Karp, H. Dr. Karp On Parenting And The Science Of Sleep. npr.org 2012; Available from: https://www.npr.org/2012/06/24/155426534/dr-karp-on-parenting-and-the-science-of-sleep.
  5. Gross, G., T. Waks, and Z. Eshhar, Expression of immunoglobulin-T-cell receptor chimeric molecules as functional receptors with antibody-type specificity. Proc Natl Acad Sci U S A, 1989. 86(24): p. 10024-8. 10.1073/pnas.86.24.10024
  6. Eshhar, Z., From the mouse cage to human therapy: a personal perspective of the emergence of T-bodies/chimeric antigen receptor T cells. Hum Gene Ther, 2014. 25(9): p. 773-8. 10.1089/hum.2014.2532
  7. Query to Clinicaltrials.gov: COVID mesenchymal, interventional. clinicaltrials.gov 2020; Available from: https://clinicaltrials.gov/ct2/results?cond=COVID&term=mesenchymal&cntry=&state=&city=&dist=&Search=Search&type=Intr.
  8. Hildreth, C. COVID-19 News: Role of Cell Therapies in COVID-19 Complications. BioInformant 2020; Available from: https://bioinformant.com/covid-19-cell-therapies/.
  9. Hildreth, C. Pluristem Treated First Three COVID-19 Patients in Israel under Compassionate Use. BioInformant 2020; Available from: https://bioinformant.com/pluristem-covid19-treatment/.
  10. Hildreth, C. Mesoblast To Evaluate Anti-Inflammatory Cell Therapy Remestemcel-L For Treatment Of COVID-19 Lung Disease. Bioinformant 2020; Available from: https://bioinformant.com/mesoblast-remestemcel-l-covid-19/.
  11. Hildreth, C. Athersys Milestones Related to ARDS. BioInformant 2020; Available from: https://bioinformant.com/athersys-barda-covid-19/.
  12. Hildreth, C. FDA Approves Phase II Trial of Hope Biosciences’ MSCs Against COVID-19. BioInformant 2020; Available from: https://bioinformant.com/hope-bio-adipose-mscs-covid19/.
  13. Hildreth, C. Stem Cells for Coronavirus: Could Cells Be The Cure? BioInformant 2020; Available from: https://bioinformant.com/stem-cells-coronavirus/.
  14. Zikuan Leng, R.Z., Wei Hou, Yingmei Feng, Yanlei Yang, Qin Han, Guangliang Shan, Fanyan Meng, Dongshu Du, Shihua Wang, Junfen Fan, Wenjing Wang, Luchan Deng, Hongbo Shi, Hongjun Li, Zhongjie Hu, Fengchun Zhang, Jinming Gao, Hongjian Liu, Xiaoxia Li, Yangyang Zhao, Kan Yin, Xijing He, Zhengchao Gao, Yibin Wang, Bo Yang, Ronghua Jin, Ilia Stambler, Lee Wei Lim, Huanxing Su, Alexey Moskalev, Antonio Cano, Sasanka Chakrabarti, Kyung-Jin Min, Georgina Ellison-Hughes, Calogero Caruso, Kunlin Jin, Robert Chunhua Zhao, Transplantation of ACE2- Mesenchymal Stem Cells Improves the Outcome of Patients with COVID-19 Pneumonia. Aging and disease: p. 216-228. 10.14336/ad.2020.0228
  15. Williams, R. Are Mesenchymal Stem Cells a Promising Treatment for COVID-19? The Scientist 2020; Available from: https://www.the-scientist.com/news-opinion/are-mesenchymal-stem-cells-a-promising-treatment-for-covid-19–67402
  16. Calfee, C.S. The Acute Respiratory Distress Syndrome and Treatment with Mesenchymal Stem Cells, Part 1. 2013; Available from: https://youtu.be/SpqFFpmrtmY.
  17. Matthay, M.A. The Acute Respiratory Distress Syndrome and Treatment with Mesenchymal Stem Cells, Part 2. 2013; Available from: https://youtu.be/v3tbwhu3Xio.
  18. Frank, J.A., et al., Physiological and biochemical markers of alveolar epithelial barrier dysfunction in perfused human lungs. Am J Physiol Lung Cell Mol Physiol, 2007. 293(1): p. L52-9. 10.1152/ajplung.00256.2006
  19. Gupta, N., et al., Intrapulmonary delivery of bone marrow-derived mesenchymal stem cells improves survival and attenuates endotoxin-induced acute lung injury in mice. J Immunol, 2007. 179(3): p. 1855-63. 10.4049/jimmunol.179.3.1855
  20. Lee, J.W., et al., Allogeneic human mesenchymal stem cells for treatment of E. coli endotoxin-induced acute lung injury in the ex vivo perfused human lung. Proc Natl Acad Sci U S A, 2009. 106(38): p. 16357-62. 10.1073/pnas.0907996106
  21. Gupta, N., et al., Mesenchymal stem cells enhance survival and bacterial clearance in murine Escherichia coli pneumonia. Thorax, 2012. 67(6): p. 533-9. 10.1136/thoraxjnl-2011-201176
  22. Krasnodembskaya, A., et al., Human mesenchymal stem cells reduce mortality and bacteremia in gram-negative sepsis in mice in part by enhancing the phagocytic activity of blood monocytes. Am J Physiol Lung Cell Mol Physiol, 2012. 302(10): p. L1003-13. 10.1152/ajplung.00180.2011
  23. Lee, J.W., et al., Therapeutic effects of human mesenchymal stem cells in ex vivo human lungs injured with live bacteria. Am J Respir Crit Care Med, 2013. 187(7): p. 751-60. 10.1164/rccm.201206-0990OC
  24. Asmussen, S., et al., Human mesenchymal stem cells reduce the severity of acute lung injury in a sheep model of bacterial pneumonia. Thorax, 2014. 69(9): p. 819-25. 10.1136/thoraxjnl-2013-204980
  25. Matthay, M.A., et al., Treatment with allogeneic mesenchymal stromal cells for moderate to severe acute respiratory distress syndrome (START study): a randomised phase 2a safety trial. Lancet Respir Med, 2019. 7(2): p. 154-162. 10.1016/S2213-2600(18)30418-1
  26. Matthay, M.A., Therapeutic potential of mesenchymal stromal cells for acute respiratory distress syndrome. Ann Am Thorac Soc, 2015. 12 Suppl 1: p. S54-7. 10.1513/AnnalsATS.201406-254MG
  27. Lim M, C.J., Rowley JA. hMSCs: A Secret(ome) Weapon Against ARDS. RoosterBio 2020; Available from: hMSCs: A Secret(ome) Weapon Against ARDS.
  28. Worthington, E.N. and J.S. Hagood, Therapeutic Use of Extracellular Vesicles for Acute and Chronic Lung Disease. Int J Mol Sci, 2020. 21(7). 10.3390/ijms21072318
  29. Liu, A., et al., Therapeutic potential of mesenchymal stem/stromal cell-derived secretome and vesicles for lung injury and disease. Expert Opin Biol Ther, 2020. 20(2): p. 125-140. 10.1080/14712598.2020.1689954
  30. Abraham, A. and A. Krasnodembskaya, Mesenchymal stem cell-derived extracellular vesicles for the treatment of acute respiratory distress syndrome. Stem Cells Transl Med, 2020. 9(1): p. 28-38. 10.1002/sctm.19-0205
  31. Hospital, R., et al., A Pilot Clinical Study on Inhalation of Mesenchymal Stem Cells Exosomes Treating Severe Novel Coronavirus Pneumonia. 2020, https://ClinicalTrials.gov/show/NCT04276987.
  32. ChiCTR2000030261, A study for the key technology of mesenchymal stem cells exosomes atomization in the treatment of novel coronavirus pneumonia (COVID-19). 2020.
  33. McShane, L.M., et al., Criteria for the use of omics-based predictors in clinical trials. Nature, 2013. 502(7471): p. 317-20. 10.1038/nature12564
  34. Webb-Robertson, B.J., et al., Sequential projection pursuit principal component analysis–dealing with missing data associated with new -omics technologies. Biotechniques, 2013. 54(3): p. 165-8. 10.2144/000113978
  35. Aquatic ape hypothesis. wikipedia.org 2020; Available from: https://en.wikipedia.org/wiki/Aquatic_ape_hypothesis.
  36. Savannah hypothesis. wikipedia.org 2020; Available from: https://en.wikipedia.org/wiki/Savannah_hypothesis.
  37. K.Williams and C. Hansen. Quality Begins at Inception. RoosterBio Blog 2020; Available from: https://www.roosterbio.com/quality-regulatory/quality-begins-at-inception/.
  38. J. Takacs and K. Adlerz. UC-MSC Exhibit Robust Proliferation in 3D Bioreactor System. RoosterBio Blog 2020; Available from: https://www.roosterbio.com/cell-therapy/huc-msc-exhibit-robust-proliferation-in-3d-bioreactor-system/.
  39. Adlerz, K. Generating MSC-EVs With a Scalable Manufacturing System. RoosterBio Blog 2020; Available from: https://www.roosterbio.com/evs-exosomes/generating-msc-evs-with-a-scalable-manufacturing-system/.
  40. Grupp, S.A., et al., Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med, 2013. 368(16): p. 1509-1518. 10.1056/NEJMoa1215134
  41. Caplan, A.I. and D. Correa, The MSC: an injury drugstore. Cell Stem Cell, 2011. 9(1): p. 11-5. 10.1016/j.stem.2011.06.008
  42. Hay, M., et al., Clinical development success rates for investigational drugs. Nat Biotechnol, 2014. 32(1): p. 40-51. 10.1038/nbt.2786
  43. Yang, X., et al., Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med, 2020. 10.1016/S2213-2600(20)30079-5
  44. Angelini, D.J., et al., Chemical warfare agent and biological toxin-induced pulmonary toxicity: could stem cells provide potential therapies? Inhal Toxicol, 2013. 25(1): p. 37-62. 10.3109/08958378.2012.750406
  45. Matthay, M.A. and R.L. Zemans, The acute respiratory distress syndrome: pathogenesis and treatment. Annu Rev Pathol, 2011. 6: p. 147-63. 10.1146/annurev-pathol-011110-130158
  46. Wilson, J.G. and C.S. Calfee, ARDS Subphenotypes: Understanding a Heterogeneous Syndrome. Crit Care, 2020. 24(1): p. 102. 10.1186/s13054-020-2778-x
  47. Jon Carson, I.F., John Getz, and Jon A. Rowley. Scalable MSC Manufacturing Matters in a Rapid Response to COVID-19. RoosterBio Blog 2020; Available from: https://www.roosterbio.com/biomanufacturing/scalable-msc-manufacturing-matters-in-a-rapid-response-to-covid-19/.
  48. Han, J., Y. Li, and Y. Li, Strategies to Enhance Mesenchymal Stem Cell-Based Therapies for Acute Respiratory Distress Syndrome. Stem Cells Int, 2019. 2019: p. 5432134. 10.1155/2019/5432134
  49. Kojima, R., L. Scheller, and M. Fussenegger, Nonimmune cells equipped with T-cell-receptor-like signaling for cancer cell ablation. Nat Chem Biol, 2018. 14(1): p. 42-49. 10.1038/nchembio.2498
  50. Abbott, T.R., et al., Development of CRISPR as a prophylactic strategy to combat novel coronavirus and influenza. bioRxiv, 2020: p. 2020.03.13.991307. 10.1101/2020.03.13.991307
  51. Maguire, C.A., et al., Microvesicle-associated AAV vector as a novel gene delivery system. Mol Ther, 2012. 20(5): p. 960-71. 10.1038/mt.2011.303
  52. Alvarez-Erviti, L., et al., Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol, 2011. 29(4): p. 341-5. 10.1038/nbt.1807
  53. Gulei, D. and I. Berindan-Neagoe, Activation of Necroptosis by Engineered Self Tumor-Derived Exosomes Loaded with CRISPR/Cas9. Mol Ther Nucleic Acids, 2019. 17: p. 448-451. 10.1016/j.omtn.2019.05.032

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