Robert E. Donahue
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View article: The Impact of CD45-Antibody-Drug Conjugate Conditioning on Clonal Dynamics and Immune Tolerance Post HSPC Transplantation in Rhesus Macaques
The Impact of CD45-Antibody-Drug Conjugate Conditioning on Clonal Dynamics and Immune Tolerance Post HSPC Transplantation in Rhesus Macaques Open
Compared to total body irradiation (TBI) or chemotherapy, antibody-drug conjugate (ADC) transplant conditioning may offer a more targeted and less toxic approach to clearing bone marrow niches to permit robust hematopoietic stem progenitor…
View article: Fertility-preserving myeloablative conditioning using single-dose CD117 antibody-drug conjugate in a rhesus gene therapy model
Fertility-preserving myeloablative conditioning using single-dose CD117 antibody-drug conjugate in a rhesus gene therapy model Open
Hematopoietic stem cell (HSC) gene therapy has curative potential; however, its use is limited by the morbidity and mortality associated with current chemotherapy-based conditioning. Targeted conditioning using antibody-drug conjugates (AD…
View article: CD3-immunotoxin mediated depletion of T cells in lymphoid tissues of rhesus macaques
CD3-immunotoxin mediated depletion of T cells in lymphoid tissues of rhesus macaques Open
Selective T-cell depletion prior to cell or organ transplantation is considered a preconditioning regimen to induce tolerance and immunosuppression. An immunotoxin consisting of a recombinant anti-CD3 antibody conjugated with diphtheria to…
View article: Forced enhancer-promoter rewiring to alter gene expression in animal models
Forced enhancer-promoter rewiring to alter gene expression in animal models Open
Transcriptional enhancers can be in physical proximity of their target genes via chromatin looping. The enhancer at the β-globin locus (locus control region [LCR]) contacts the fetal-type (HBG) and adult-type (HBB) β-globin genes during co…
View article: Intrabone transplantation of CD34+ cells with optimized delivery does not enhance engraftment in a rhesus macaque model
Intrabone transplantation of CD34+ cells with optimized delivery does not enhance engraftment in a rhesus macaque model Open
Intrabone (IB) injection of umbilical cord blood has been proposed as a potential mechanism to improve transplant engraftment and prevent graft failure. However, conventional IB techniques produce low retention of transplanted cells in the…
View article: NADPH oxidase correction by mRNA transfection of apheresis granulocytes in chronic granulomatous disease
NADPH oxidase correction by mRNA transfection of apheresis granulocytes in chronic granulomatous disease Open
Granulocytes from patients with chronic granulomatous disease (CGD) have dysfunctional phagocyte reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase that fails to generate sufficient antimicrobial reactive oxidative species…
View article: BCL11A enhancer–edited hematopoietic stem cells persist in rhesus monkeys without toxicity
BCL11A enhancer–edited hematopoietic stem cells persist in rhesus monkeys without toxicity Open
Gene editing of the erythroid-specific BCL11A enhancer in hematopoietic stem and progenitor cells (HSPCs) from patients with sickle cell disease (SCD) induces fetal hemoglobin (HbF) without detectable toxicity, as assessed by mouse xenotra…
View article: A Single Dose of CD117 Antibody Drug Conjugate Enables Hematopoietic Stem Cell Based Gene Therapy in Nonhuman Primates
A Single Dose of CD117 Antibody Drug Conjugate Enables Hematopoietic Stem Cell Based Gene Therapy in Nonhuman Primates Open
Autologous hematopoietic stem cell transplantation (Auto-HSCT) with gene-modification represents a potential cure for multiple genetic diseases, but its broad curative potential, is limited because of morbidity/mortality from cytotoxic che…
View article: A Practitioner's Perspective on Institutionalizing Voter Registration on College & University Campuses
A Practitioner's Perspective on Institutionalizing Voter Registration on College & University Campuses Open
For the past decade, Northwestern University has implemented an initiative which has resulted in a voter registration rate averaging around 90% of its entire eligible student body. Meanwhile, this concentrated effort to integrate comprehen…
View article: Impact of CMV Infection on Natural Killer Cell Clonal Repertoire in CMV-Naïve Rhesus Macaques
Impact of CMV Infection on Natural Killer Cell Clonal Repertoire in CMV-Naïve Rhesus Macaques Open
Recent functional, gene expression, and epigenetic studies have suggested the presence of a subset of mature natural killer (NK) cells responsible for maintaining NK cell memory. The lack of endogenous clonal markers in NK cells impedes un…
View article: Clonal tracking of erythropoiesis in rhesus macaques
Clonal tracking of erythropoiesis in rhesus macaques Open
The classical model of hematopoietic hierarchies is being reconsidered on the basis of data from in vitro assays and single cell expression profiling. Recent experiments suggested that the erythroid lineage might differentiate directly fro…
View article: Development of a forward-oriented therapeutic lentiviral vector for hemoglobin disorders
Development of a forward-oriented therapeutic lentiviral vector for hemoglobin disorders Open
Hematopoietic stem cell (HSC) gene therapy is being evaluated for hemoglobin disorders including sickle cell disease (SCD). Therapeutic globin vectors have demanding requirements including high-efficiency transduction at the HSC level and …
View article: Busulfan Combined with Immunosuppression Allows Efficient Engraftment of Gene-Modified Cells in a Rhesus Macaque Model
Busulfan Combined with Immunosuppression Allows Efficient Engraftment of Gene-Modified Cells in a Rhesus Macaque Model Open
Busulfan conditioning is utilized for hematopoietic stem cell (HSC) depletion in the context of HSC gene-therapy conditioning but may result in insufficient immunosuppression. In this study, we evaluated whether additional immunosuppressio…
View article: CRISPR/Cas9 PIG-A gene editing in nonhuman primate model demonstrates no intrinsic clonal expansion of PNH HSPCs
CRISPR/Cas9 PIG-A gene editing in nonhuman primate model demonstrates no intrinsic clonal expansion of PNH HSPCs Open
Recent advances in gene editing technologies using CRISPR/ Cas9 allow precise genome editing at a site of interest and have accelerated human disease modeling and the development of corrective gene therapies for various genetic disorders. …
View article: Aberrant Clonal Hematopoiesis Following Lentiviral Transduction of HSPC in a Rhesus Macaque
Aberrant Clonal Hematopoiesis Following Lentiviral Transduction of HSPC in a Rhesus Macaque Open
Lentiviral vectors (LV) have been used for the delivery of genes into hematopoietic stem and progenitor cells (HSPC) in clinical trials worldwide. LV, in contrast to retroviral vectors, have not been associated with insertion site-associat…
View article: Clonal expansion and compartmentalized maintenance of rhesus macaque NK cell subsets
Clonal expansion and compartmentalized maintenance of rhesus macaque NK cell subsets Open
Macaque barcoding reveals NK oligoclonal expansion and persistence independent of production from HSPCs or immature NK cells.
View article: Barcoding of Macaque Hematopoietic Stem and Progenitor Cells: A Robust Platform to Assess Vector Genotoxicity
Barcoding of Macaque Hematopoietic Stem and Progenitor Cells: A Robust Platform to Assess Vector Genotoxicity Open
Gene therapies using integrating retrovirus vectors to modify hematopoietic stem and progenitor cells have shown great promise for the treatment of immune system and hematologic diseases. However, activation of proto-oncogenes via insertio…
View article: The impact of aging on primate hematopoiesis as interrogated by clonal tracking
The impact of aging on primate hematopoiesis as interrogated by clonal tracking Open
Key Points Genetic barcoding of HSPCs in aged macaques reveals impaired long-term clonal output from multipotent HSPCs. Aged macaques showed prolonged contributions from lineage-biased HSPCs and late clonal expansions.
View article: Geographic clonal tracking in macaques provides insights into HSPC migration and differentiation
Geographic clonal tracking in macaques provides insights into HSPC migration and differentiation Open
The geographic distribution of hematopoiesis at a clonal level is of interest in understanding how hematopoietic stem and progenitor cells (HSPCs) and their progeny interact with bone marrow (BM) niches during regeneration. We tagged rhesu…
View article: CD4+ levels control the odds of induction of humoral immune responses to tracer doses of therapeutic antibodies
CD4+ levels control the odds of induction of humoral immune responses to tracer doses of therapeutic antibodies Open
Rapidly increasing number of therapeutic antibodies are being repurposed to imaging probes for noninvasive diagnosis, as well as monitoring during treatment or disease recurrence. Though antibody-based imaging involves tracer doses (~3 log…
View article: Bone Marrow as a Hematopoietic Stem Cell Source for Gene Therapy in Sickle Cell Disease: Evidence from Rhesus and SCD Patients
Bone Marrow as a Hematopoietic Stem Cell Source for Gene Therapy in Sickle Cell Disease: Evidence from Rhesus and SCD Patients Open
Steady state bone marrow (BM) is the preferred hematopoietic stem cell (HSC) source for gene therapy in sickle cell disease (SCD) due to the recognized risk of vaso-occlusive crisis during granulocyte colony-stimulating factor mobilization…
View article: Quantitative stability of hematopoietic stem and progenitor cell clonal output in rhesus macaques receiving transplants
Quantitative stability of hematopoietic stem and progenitor cell clonal output in rhesus macaques receiving transplants Open
Key Points Output from individual rhesus macaque hematopoietic stem and progenitor cells is stable for years, with little evidence of clonal succession. Individual clones may display stable myeloid or lymphoid bias for many years.