Evidence map›Paper›PMID 38074899›Full record

ArticleMolecular therapy. Nucleic acids2023

A bimolecular modification strategy for developing long-lasting bone anabolic aptamer.

Huarui Zhang, Sifan Yu, Shuaijian Ni, Amu Gubu, Yuan Ma, Yihao Zhang, Haitian Li, Yuzhe Wang, Luyao Wang, Zongkang Zhang and 4 more

Open access · goldAbstract read
In one paragraph

Article in Molecular therapy. Nucleic acids, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
1.8field-weighted citation impact, top 14% of its field
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

14 citing papers in PubMed, 12 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Review
  14. 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

14 authors at 4 institutions in 3 countries.

Huarui ZhangSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Sifan YuSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Shuaijian NiShenzhen Research Institute, The Chinese University of Hong Kong, Shenzhen, China.
Amu GubuLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, Hong Kong Baptist University, Hong Kong SAR, China.
Yuan MaLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, Hong Kong Baptist University, Hong Kong SAR, China.
Yihao ZhangSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Haitian LiLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, Hong Kong Baptist University, Hong Kong SAR, China.
Yuzhe WangThe Second Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou, China.
Luyao WangLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, Hong Kong Baptist University, Hong Kong SAR, China.
Zongkang ZhangSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Yuanyuan YuLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, Hong Kong Baptist University, Hong Kong SAR, China.
Aiping LyuLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, Hong Kong Baptist University, Hong Kong SAR, China.
Baoting ZhangSchool of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Ge ZhangLaw Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, Hong Kong Baptist University, Hong Kong SAR, China.
Hong Kong Baptist University · HKChinese University of Hong Kong · HKChinese University of Hong Kong, Shenzhen · CNFirst Affiliated Hospital of Henan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The molecular weight of nucleic acid aptamers (20 kDa) is lower than the cutoff threshold of the renal filtration (30-50 kDa), resulting in a very short half-life, which dramatically limits their druggability. To address this, we utilized 3-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)-N-(4-hydroxy-2-oxo-2H-chromen-6-yl)propenamide (HC) and 12-((2,5-dioxopyrrolidin-1-yl)oxy)-12-oxododecanoic acid (DA), two newly designed coupling agents, for synergistic binding to human serum albumin (HSA). Both HC and DA are conjugated to a bone anabolic aptamer (Apc001) against sclerostin to form an Apc001OC conjugate with high binding affinity to HSA. Notably, HC and DA could synergistically facilitate prolonging the half-life of the conjugated Apc001 and promoting its bone anabolic potential. Using the designed blocking peptides, the mechanism studies indicate that the synergistic effect of HC-DA on pharmacokinetics and bone anabolic potential of the conjugated Apc001 is achieved via their synergistic binding to HSA. Moreover, biweekly Apc001OC at 50 mg/kg shows comparable bone anabolic potential to the marketed sclerostin antibody given weekly at 25 mg/kg. This proposed bimolecular modification strategy could help address the druggability challenge for aptamers with a short half-life.

Indexed as

aptamerslong-lasting modificationlow-molecular-weight coupling agentsMT: Oligonucleotides: Therapies and Applicationsosteogenesis imperfectasclerostin

Identifiers

PMID38074899
PMCPMC10709176
OpenAlexW4388570138

What Socratic holds

Textmetadata
LicenceCC BY
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.