Evidence map›Paper›PMID 39920120›Full record

ArticleNature communications2025

Base editing HbS to HbG-Makassar improves hemoglobin function supporting its use in sickle cell disease.

Zachary Kostamo, Manuel A Ortega, Chavonna Xu, Patricia R Feliciano, Elizabeth Budak, Daisy Lam, Valerie Winton, Rebecca Jenkins, Archita Venugopal, Margaret Zhang and 17 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
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

27 authors.

Zachary Kostamo *Emory University School of Medicine, Department of Pediatrics, Atlanta, GA, USA.
Manuel A Ortega *Beam Therapeutics, Cambridge, MA, USA. mortega@beamtx.com.ORCID http://orcid.org/0000-0003-2213-9516
Chavonna XuBeam Therapeutics, Cambridge, MA, USA.
Patricia R FelicianoBeam Therapeutics, Cambridge, MA, USA.
Elizabeth BudakBeam Therapeutics, Cambridge, MA, USA.ORCID http://orcid.org/0009-0003-1558-511X
Daisy LamBeam Therapeutics, Cambridge, MA, USA.
Valerie WintonBeam Therapeutics, Cambridge, MA, USA.
Rebecca JenkinsBeam Therapeutics, Cambridge, MA, USA.
Archita VenugopalBeam Therapeutics, Cambridge, MA, USA.
Margaret ZhangBeam Therapeutics, Cambridge, MA, USA.
John JamiesonBeam Therapeutics, Cambridge, MA, USA.
Brent CoismanBeam Therapeutics, Cambridge, MA, USA.
Kennedy GoldsboroughEmory University School of Medicine, Department of Pediatrics, Atlanta, GA, USA.
Britney HernandezEmory University School of Medicine, Department of Pediatrics, Atlanta, GA, USA.
Celeste K KanneEmory University School of Medicine, Department of Pediatrics, Atlanta, GA, USA.ORCID http://orcid.org/0009-0002-0547-905X
Erica N EvansEmory University School of Medicine, Department of Pediatrics, Atlanta, GA, USA.
Jordan ZgodnyEmory University School of Medicine, Department of Pediatrics, Atlanta, GA, USA.
Yankai ZhangEmory University School of Medicine, Department of Pediatrics, Atlanta, GA, USA.
Jawa DarazimEmory University School of Medicine, Department of Pediatrics, Atlanta, GA, USA.
Ashwin PatelEmory University School of Medicine, Department of Pediatrics, Atlanta, GA, USA.ORCID http://orcid.org/0000-0003-0075-3304
Michael A PendergastEmory University School of Medicine, Department of Pediatrics, Atlanta, GA, USA.ORCID http://orcid.org/0009-0000-3560-0290
John ManisJoint Program in Transfusion Medicine, Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-3630-778X
Adam J HartiganBeam Therapeutics, Cambridge, MA, USA.
Giuseppe CiaramellaBeam Therapeutics, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3339-7211
Seung-Joo LeeBeam Therapeutics, Cambridge, MA, USA.
S Haihua ChuBeam Therapeutics, Cambridge, MA, USA. hchu@beamtx.com.ORCID http://orcid.org/0000-0002-8333-5409
Vivien A SheehanEmory University School of Medicine, Department of Pediatrics, Atlanta, GA, USA. vivien.sheehan@emory.edu.ORCID http://orcid.org/0000-0003-2837-2255

Funding

X-ray Scattering Technology CoreP30GM133893 · NIGMS · BROOKHAVEN SCIENCE ASSOC-BROOKHAVEN LAB · PI Vivian Stojanoff · 2019 to 2026
$38.6M
NIGMS NIH HHS P30 GM133893U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS) P30GM133893
6 · The paper itself

Abstract

Adenine base editing can convert sickle hemoglobin (HbS, βΕ6V) to G-Makassar hemoglobin (HbG, βE6A), a naturally occurring variant that is clinically asymptomatic. However, the quality and functionality of purified HbG and of mature HbGG and HbGS red blood cells (RBC) has not been assessed. Here, we develop a mouse model to characterize HbG. Purified HbG appears normal and does not polymerize under hypoxia. The topology of the hemoglobin fold with the βΕ6Α mutation is similar to HbA in the oxy and deoxy states. However, RBC containing HbGS are dehydrated, showing altered function and increased sickling under hypoxia. Blood counts and mitochondrial retention measures place HbGS RBCs as intermediate in severity between HbAS and HbSS, while organ function is comparable to HbAS. HbGG resembles HbAA for most metrics. Our results highlight the importance of functionally assessing the mature red cell environment when evaluating novel gene editing strategies for hematologic disorders.

Indexed as

Anemia, Sickle CellGene EditingHemoglobins, AbnormalHemoglobin, SickleAnimalsDisease Models, AnimalErythrocytesFemaleHumansMaleMiceMice, Inbred C57BLMutationHemoglobins, AbnormalHemoglobin, Sickle

Identifiers

PMID39920120
PMCPMC11806015

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.