Evidence map›Paper›PMID 38938759›Full record

ArticleMolecular therapy. Nucleic acids2024

Phosphatidylcholine head group chemistry alters the extrahepatic accumulation of lipid-conjugated siRNA.

Vignesh N Hariharan, Takahiro Nakamura, Minwook Shin, Qi Tang, Vyankat Sontakke, Jillian Caiazzi, Samuel Hildebrand, Anastasia Khvorova, Ken Yamada

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy. Nucleic acids, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

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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

1 citing paper in PubMed.

  1. 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

9 authors.

Vignesh N HariharanRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Takahiro NakamuraRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Minwook ShinRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Qi TangRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Vyankat SontakkeRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Jillian CaiazziRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Samuel HildebrandRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Anastasia KhvorovaRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.
Ken YamadaRNA Therapeutics Institute, University of Massachusetts Chan Medical School, Worcester, MA 01605, USA.

Funding

Chemical engineering of therapeutic RNAs for extrahepatic deliveryR35GM131839 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI ANASTASIA KHVOROVA · 2019 to 2026
$3.1M
NIGMS NIH HHS R35 GM131839
6 · The paper itself

Abstract

Small interfering RNAs (siRNAs) are revolutionizing the treatment of liver-associated indications. Yet, robust delivery to extrahepatic tissues remains a challenge. Conjugating lipids (e.g., docosanoic acid [DCA]) to siRNA supports extrahepatic delivery, but tissue accumulation remains lower than that achieved in liver by approved siRNA therapeutics. Early evidence suggests that functionalizing DCA with a head group (e.g., phosphatidylcholine [PC]) may enhance delivery to certain tissues. Here, we report the first systematic evaluation of the effect of PC head group chemistry on the extrahepatic distribution of DCA-conjugated siRNAs. We show that functionalizing DCA with a PC head group enhances siRNA accumulation in heart, muscle, lung, pancreas, duodenum, urinary bladder, and fat. Varying the size of the linker between the phosphate and choline moiety of the PC head group altered the extrahepatic accumulation of siRNA, with the optimal linker length being different for different tissues. Increasing PC head group valency also improved extrahepatic accumulation in a tissue-specific manner. This study demonstrates the structural impact of the PC moiety on the biodistribution of lipid-conjugated siRNA and introduces multiple novel PC variants for the chemical optimization of DCA-conjugated siRNA. These chemical variants can be used in the context of other lipids to increase the repertoire of conjugates for the extrahepatic distribution of siRNAs.

Indexed as

chemical structureextrahepatic deliverylipid-conjugated siRNAMT: Oligonucleotides: Therapies and Applicationsphosphocholine head groupRNA interference

Identifiers

PMID38938759
PMCPMC11209015

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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.