Evidence map›Paper›PMID 42050721›Full record

ReviewBiomarker research2026

Targeted protein degradation for fetal hemoglobin induction: a new paradigm in β-hemoglobinopathy therapy.

Sanjana Arji, Ziyang Shen, Sabrina Welch, Fadila ElMahdaoui, Ayana Bahadur, Ernie Lee, Hannah Lee, Shang-Chuen Peter Wu, Ekaterina Konshina, Burhanudin Ayubali and 3 more

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Biomarker research, 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.

Sanjana ArjiDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Ziyang ShenDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Sabrina WelchDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Fadila ElMahdaouiDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Ayana BahadurDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Ernie LeeUniversity of California, Los Angeles, CA, USA.
Hannah LeeDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Shang-Chuen Peter WuDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Ekaterina KonshinaDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Burhanudin AyubaliDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Daniel TenenHarvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.
Li ChaiDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA. lchai@bwh.harvard.edu.
Jun LiuDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA. jliu71@bwh.harvard.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

β-Hemoglobinopathies, such as β-thalassemia and sickle cell disease, are a group of genetic blood disorders that are prevalent worldwide. These conditions are characterized by defective adult hemoglobin arising from β-globin gene mutations, leading to complications such as anemia and organ damage. Treatments (e.g., pharmaceutical γ-globin inducers, blood transfusions, stem cell transplants) and curative gene therapies are available to treat these disorders. However, their use is constrained by effectiveness, tolerability, and/or substantial resource demands. Targeted protein degraders (TPDs) are therapeutic modalities that harness cellular degradation pathways to eliminate disease‑relevant proteins, encompassing both small‑molecule approaches such as PROTACs and molecular glues, and emerging antibody- and nanobody-based degraders, with the potential to provide durable treatment with scalable manufacturing. Many TPDs for β-hemoglobinopathies target transcription factors known to repress γ-globin, thereby increasing fetal hemoglobin, a hemoglobin subtype that exhibits compensatory properties. This review examines the various γ-globin-inducing TPDs currently in development, their respective advantages and limitations. We also explore TPDs’ mechanisms of actions and emerging tools that could guide future research and development.

Indexed as

Fetal hemoglobinMolecular glueNanobodyPROTACSickle cell diseaseTargeted protein degradationTreatment optionsβ-hemoglobinopathyβ-thalassemiaγ-globin

Identifiers

PMID42050721
PMCPMC13242661

What Socratic 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 Socratic graph.