Evidence map›Paper›PMID 31127296›Full record

ArticleNucleic acids research2019

Fatty acid conjugation enhances potency of antisense oligonucleotides in muscle.

Thazha P Prakash, Adam E Mullick, Richard G Lee, Jinghua Yu, Steve T Yeh, Audrey Low, Alfred E Chappell, Michael E Østergaard, Sue Murray, Hans J Gaus and 2 more

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed
5.5field-weighted citation impact, top 3% 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

99 citing papers in PubMed, 143 citations in OpenAlex.

  1. An RNA thermogenic therapy to preserve lean mass and enhance metabolic health during GLP-1 weight loss.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  8. The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026
    Review
  9. Investigating theBioconjugate chemistry · 2026
    Article
  10. Article
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  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article

39 more citing papers are in PubMed but not listed here.

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

12 authors at 1 institution in 1 country.

Thazha P PrakashIonis Pharmaceuticals, Medicinal Chemistry, USA.
Adam E MullickAntisense Drug Discovery, 2855 Gazelle Ct., Carlsbad, CA 92010, USA.
Richard G LeeAntisense Drug Discovery, 2855 Gazelle Ct., Carlsbad, CA 92010, USA.
Jinghua YuIonis Pharmaceuticals, Medicinal Chemistry, USA.
Steve T YehAntisense Drug Discovery, 2855 Gazelle Ct., Carlsbad, CA 92010, USA.
Audrey LowAntisense Drug Discovery, 2855 Gazelle Ct., Carlsbad, CA 92010, USA.
Alfred E ChappellIonis Pharmaceuticals, Medicinal Chemistry, USA.
Michael E ØstergaardIonis Pharmaceuticals, Medicinal Chemistry, USA.
Sue MurrayAntisense Drug Discovery, 2855 Gazelle Ct., Carlsbad, CA 92010, USA.
Hans J GausIonis Pharmaceuticals, Medicinal Chemistry, USA.
Eric E SwayzeIonis Pharmaceuticals, Medicinal Chemistry, USA.
Punit P SethIonis Pharmaceuticals, Medicinal Chemistry, USA.
Ionis Pharmaceuticals (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Enhancing the functional uptake of antisense oligonucleotide (ASO) in the muscle will be beneficial for developing ASO therapeutics targeting genes expressed in the muscle. We hypothesized that improving albumin binding will facilitate traversal of ASO from the blood compartment to the interstitium of the muscle tissues to enhance ASO functional uptake. We synthesized structurally diverse saturated and unsaturated fatty acid conjugated ASOs with a range of hydrophobicity. The binding affinity of ASO fatty acid conjugates to plasma proteins improved with fatty acid chain length and highest binding affinity was observed with ASO conjugates containing fatty acid chain length from 16 to 22 carbons. The degree of unsaturation or conformation of double bond appears to have no influence on protein binding or activity of ASO fatty acid conjugates. Activity of fatty acid ASO conjugates correlated with the affinity to albumin and the tightest albumin binder exhibited the highest activity improvement in muscle. Palmitic acid conjugation increases ASO plasma Cmax and improved delivery of ASO to interstitial space of mouse muscle. Conjugation of palmitic acid improved potency of DMPK, Cav3, CD36 and Malat-1 ASOs (3- to 7-fold) in mouse muscle. Our approach provides a foundation for developing more effective therapeutic ASOs for muscle disorders.

Indexed as

AnimalsBlood ProteinsCaveolin 3CD36 AntigensFatty AcidsFatty Acids, UnsaturatedMaleMice, Inbred C57BLMuscle, SkeletalMyocardiumMyotonin-Protein KinaseOligonucleotides, AntisensePalmitic AcidRNA, Long NoncodingStructure-Activity RelationshipBlood ProteinsCav3 protein, mouseCaveolin 3CD36 AntigensDMPK protein, mouseFatty AcidsFatty Acids, UnsaturatedMalat1 long non-coding RNA, mouseMyotonin-Protein KinaseOligonucleotides, AntisensePalmitic AcidRNA, Long Noncoding

Identifiers

PMID31127296
PMCPMC6614804
OpenAlexW2954589950

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Registered trials

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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.