HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation

Rk, Gupta; Abdul-Jawad, Sultan; McCoy, Laura E; Mok, Hoi Ping; Peppa, Dimitra; Salgado, María; Martínez-Picado, Javier; Nijhuis, Monique; Wensing, Annemarie M. J.; Lee, Helen; Grant, Paul; Nastouli, Eleni; Lambert, Jonathan; Pace, Matthew; Salasc, Fanny; Monit, Christopher; Innes, Andrew; Muir, Luke; Waters, Laura; Frater, John; Lever, Andrew; Edwards, Simon; Gabriel, Ian; Olavarría, Eduardo

doi:10.1038/s41586-019-1027-4

Cited by 502 publications

(436 citation statements)

References 29 publications

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“…Among these six cases, two patients from London and Düsseldorf have shown no viral rebound 19 and 3 months after HIV treatment interruption, respectively (Gupta et al, 2019;Jensen et al, 2019).…”

Section: Donation Probabilities)mentioning

confidence: 98%

“…At least 10 HIV patients have received CCR5∆32‐homozygous stem cell transplants so far, thereof 6, including the Berlin patient, from unrelated donors (Hütter, ). Among these six cases, two patients from London and Düsseldorf have shown no viral rebound 19 and 3 months after HIV treatment interruption, respectively (Gupta et al, ; Jensen et al, ). In four of the six unrelated donor cases, the stem cell product was provided by a DKMS donor.…”

Section: Donor Typing: Beyond the Classical Hla Locimentioning

confidence: 99%

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Immunogenetics in stem cell donor registry work: The DKMS example (Part 2)

Schmidt

Sauter

Baier

et al. 2020

Int J Immunogenetics

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DKMS is a leading stem cell donor registry with more than 9 million donors. Donor registry activities share many touch points with topics from immunogenetics or population genetics. In this two‐part review article, we deal with these aspects of donor registry work by using the example of DKMS. In the second part of the review, we focus on donor typing of non‐HLA genes, the impact of donor age, gender and CMV serostatus on donation probabilities, the identification of novel HLA, KIR and MIC alleles by high‐throughput donor typing, the activities of the Collaborative Biobank and pharmacogenetics in the donor registry context.

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Section: Donation Probabilities)mentioning

confidence: 98%

Section: Donor Typing: Beyond the Classical Hla Locimentioning

confidence: 99%

Immunogenetics in stem cell donor registry work: The DKMS example (Part 2)

Schmidt

Sauter

Baier

et al. 2020

Int J Immunogenetics

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“…We noticed that CCR5-32 mutation is found mainly in Europeans (but virtually absent in pure East Asian and African ethnicities), indicating it first occurred in Europe after the "Out of Africa" migration and was likely raised to a 10% allele frequency by the sixteenth-century Black Death and earlier bubonic plague episodes. Both the Berlin patient and London patient, the only two individuals to have had HIV cleared or cured (of the 37 million HIV carriers alive today), received a stem cell transplant using HLA-match donors who were homozygous for CCR5-32/ 32 (111)(112)(113). There are provocative reports that CCR5 action is important in graft-versus-host disease (GVHD), which can kill up to one-third of bone marrow transplant recipients in cancer therapy (114,115).…”

Section: Aids-restriction Genes and The Era Of Genome-wide Associatiomentioning

confidence: 99%

A Beautiful Life: High Risk–High Payoff in Genetic Science

O’Brien

2020

Annu. Rev. Anim. Biosci.

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Portrait by Varvara Simonov n a aAnnu. Rev. Anim. Biosci. 2020.8:1-24. Downloaded from www.annualreviews.org Access provided by 50.80.253.90 on 03/16/20. For personal use only. AbstractThis narrative is a personal view of adventures in genetic science and society that have blessed my life and career across five decades. The advances I enjoyed and the lessons I learned derive from educational training, substantial collaboration, and growing up in the genomics age. I parse the stories into six research disciplines my students, fellows, and colleagues have entered and, in some cases, made an important difference. The first is comparative genetics, where evolutionary inference is applied to genome organization, from building gene maps in the 1970s to building whole genome sequences today. The second area tracks the progression of molecular evolutionary advances and applications to resolve the hierarchical relationship among living species in the silence of prehistory. The third endeavor outlines the birth and maturation of genetic studies and application to species conservation. The fourth theme discusses how emerging viruses studied in a genomic sense opened our eyes to host-pathogen interaction and interdependence. The fifth research emphasis outlines the population genetic-based search and discovery of human restriction genes that influence the epidemiological outcome of abrupt outbreaks, notably HIV-AIDS and several cancers. Finally, the last arena explored illustrates how genetic individualization in human and animals has improved forensic evidence in capital crimes. Each discipline has intuitive and technological overlaps, and each has benefitted from the contribution of genetic and genomic principles I learned so long ago from Drosophila. The journey continues.It's a very ancient saying but a true and honest thought, that if you become a teacher, by your pupils you'll be taught.-Oscar Hammerstein II, The King and I (1951) self-trained radio engineer. He began by building crystal radio sets in the late 1920s, and with but a high school diploma, he went on to build the CBS radio station and then the TV station in Rochester, where he became chief engineer. In my early youth, I paid little attention to science, being more interested in baseball, dogs, and rock and roll. My family relocated to Bethesda, Maryland, outside Washington, DC, in 1958, where I had a rather undistinguished high school performance that, to be frank, would limit my college admission opportunities. One thing I did enjoy in that period was singing and dancing in amateur high school musicals. Looking back, I suspect that these on-stage appearances provided terrific preparation in building confidence for public speaking later in the science arena. After hitchhiking 12 miles each day to Good Counsel High School in Wheaton, Maryland, I was excited to enter St. Francis College, a small liberal arts Catholic school run by Franciscan friars in the hills of western Pennsylvania. St. Francis was good for me. It protected me from my adolescent instinc...

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“…reported a second case, the 'London Patient', who received a similar transplantation with CCR5 D32 HSPCs but using a milder conditioning regime [247]. reported a second case, the 'London Patient', who received a similar transplantation with CCR5 D32 HSPCs but using a milder conditioning regime [247].…”

Section: Hiv-1/aidsmentioning

confidence: 99%

Adenovirus vectors in hematopoietic stem cell genome editing

Lieber

2019

FEBS Letters

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Genome editing of hematopoietic stem cells (HSCs) represents a therapeutic option for a number of hematological genetic diseases, as HSCs have the potential for self-renewal and differentiation into all blood cell lineages. This review presents advances of genome editing in HSCs utilizing adenovirus vectors as delivery vehicles. We focus on capsid-modified, helper-dependent adenovirus vectors that are devoid of all viral genes and therefore exhibit an improved safety profile. We discuss HSC genome engineering for several inherited disorders and infectious diseases including hemoglobinopathies, Fanconi anemia, hemophilia, and HIV-1 infection by ex vivo and in vivo editing in transgenic mice, nonhuman primates, as well as in human CD34 + cells. Mechanisms of therapeutic gene transfer including episomal expression of designer nucleases and base editors, transposase-mediated random integration, and targeted homology-directed repair triggered integration into selected genomic safe harbor loci are also reviewed.

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HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation

Cited by 502 publications

References 29 publications

Immunogenetics in stem cell donor registry work: The DKMS example (Part 2)

Immunogenetics in stem cell donor registry work: The DKMS example (Part 2)

A Beautiful Life: High Risk–High Payoff in Genetic Science

Adenovirus vectors in hematopoietic stem cell genome editing

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