Evidence map›Paper›PMID 42785298›Full record

ArticleCell stem cell2026

Systemic delivery of phagocytosis-shielded retroviral vectors enables in vivo HSC gene therapy for sickle cell disease.

Denise Klatt, Adele Mucci, Boya Liu, Marie Peschers, Giulia Schiroli, Axel Schambach, John Manis, Myriam Armant, David T Scadden, Els Verhoeyen and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Denise KlattDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: denise.klatt@childrens.harvard.edu.
Adele MucciDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Boya LiuDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Marie PeschersDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA.
Giulia SchiroliKrantz Family Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Axel SchambachInstitute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
John ManisDepartment of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Myriam ArmantTherapeutic Innovation Lab, Boston Children's Hospital, Boston, MA 02115, USA.
David T ScaddenKrantz Family Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Els VerhoeyenCIRI - International Center for Infectiology Research, Inserm, U1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, 69007, Lyon, France; Université Côte d'Azur, Centre Méditerranéen de Médecine Moléculaire, Nice, France.
Danilo PellinDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
David A WilliamsDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA.
Christian BrendelDivision of Hematology/Oncology, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Harvard Stem Cell Institute, Cambridge, MA 02138, USA. Electronic address: christian.brendel@childrens.harvard.edu.

Funding

In vivo hematopoietic stem cell genetic modification by viral particlesR01HL172489 · NHLBI · BOSTON CHILDREN'S HOSPITAL · PI Daniel Evan Bauer, Christian Brendel · 2024 to 2026
$2.6M
Bill & Melinda Gates Foundation INV-021791NHLBI NIH HHS R01 HL172489
6 · The paper itself

Abstract

Ex vivo hematopoietic stem cell (HSC) gene therapy is effective for non-malignant blood disorders including sickle cell disease (SCD), but requires hospitalization, ex vivo cell manipulation, and conditioning. Direct in vivo gene delivery could remove these barriers and widen access. Here, we explore phagocytosis-shielded lentiviral and alpha-retroviral vectors pseudotyped with the baboon endogenous retrovirus glycoprotein variant BaEVRLess for in vivo HSC gene transfer. Vector injection into mobilized humanized mice yielded up to 8.8% gene marking in hCD45+ cells, which chemoselection enriched to 70% of hCD45+ cells and 54% of HSCs. Barcode analysis showed polyclonal reconstitution in over 90% of mice, which remained stable in secondary recipients. For SCD, we targeted BCL11A and ZNF410 selectively in erythroid cells using miRNA-embedded shRNAs to derepress gamma-globin, reaching therapeutically relevant levels of 61.5% of beta-like globins. In summary, BaEVRLess-pseudotyped lentiviral vectors enable clinically relevant in vivo gene transfer and fetal globin induction for SCD.

Indexed as

Anemia, Sickle CellGenetic TherapyGenetic VectorsGene Transfer TechniquesHematopoietic Stem CellsPhagocytosisRetroviridaeAnimalsGene Therapy AgentsHumansMicealpha-retroviral vectorbaboon endogenous retrovirus glycoproteinBaEVhematopoietic stem cellHSCin vivo gene therapylentiviral vectorSCDsickle cell disease

Identifiers

PMID42785298
PMCPMC13612944

What OpenQuestion holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.