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Formulation & In Vivo Data

Lipid P3B · DC60934 · Updated 29 October 2026

Literature evidence · DC60934

Formulation & In Vivo Data

A reference lipid for research on intrathecal mRNA delivery and functional gene editing in the central nervous system.

Formulation In vivo results Tolerability Reference

Values shown are literature-reported results for the cited formulation and study conditions. They do not guarantee performance of the supplied product in other formulations or experiments.

Formulation and particle properties

DOE-03 was selected in the reported formulation comparison. The record below separates consistent findings from unresolved composition labels.

Parameter	Literature record	Source / status
Delivery route	Intrathecal; mouse CNS research	Figures 2–5 / Reported
Study cargos	Reporter mRNA, Cas9 mRNA with guide RNA, and adenine base-editor mRNA with guide RNA	Figures 2–4 / Reported
Ionizable lipid:mRNA	10:1 by mass	Formulation optimization section / Reported; not an N/P value
N/P ratio	Unresolved	Figure 2a axis labeling requires reconciliation with the mass-ratio description
Hydrodynamic diameter / PDI	110 nm / 0.108	Formulation optimization section / Reported
LNP apparent pKa	6.51	Main text citing Figure S16; supporting assay details not independently verified
Particle morphology	Approximately spherical particles	Figure 2f / Reported
Encapsulation efficiency / zeta potential	No verified numerical value entered	Supporting information review pending

Component identity, molecular weight and reported molar fraction

Component	MW	Optimized formulation	DC Chemicals product
P3B	645.07	60 mol% reported	DC60934
DOPE	744.0478	30 mol% reported	DC33634
Cholesterol	386.65	Not assigned while PEG fraction is unresolved	DCD-041
PEG-lipid	Study identity pending; catalog DMG-PEG2000: 2507	0.5 mol% in text; 1.5% in Figure 2e	DMG-PEG2000 · DC40169

Composition review: the main text and Figure 2e disagree on PEG content. The paper also uses C14-PEG and DMG-PEG labels. A definitive four-component molar-to-mass conversion is therefore withheld. Catalog molecular weights above are reference values, not confirmation of the paper's PEG reagent identity.

Functional CNS delivery

Model and readout	Reported finding	Context
Ai9 reporter mice; Cas9-mediated reporter activation	Higher tdTomato-positive cell fractions than the MC3 comparator in the examined CNS regions	Figure 3; intrathecal; 0.05 mg/kg mRNA; repeat administration; day-14 assessment; n=3 biological replicates
LumA reporter mice; target-site base editing	P3B: 14.8%; MC3: 6.9%	Figure 4e–f; intrathecal; 0.05 mg/kg mRNA; day-20 assessment; Sanger/ EditR; n=3
Editing-rate comparison	Approximately 2.14-fold (14.8 ÷ 6.9)	Calculated from the reported editing percentages; not the luminescence ratio
Reporter signal persistence	Signal observed from day 5 through day 20	Figure 4b–c; reflects the reporter-editing experiment, not 20-day persistence of intact LNPs

These are reporter-model findings. They establish functional delivery under the studied conditions; intravenous blood–brain barrier crossing and disease-treatment efficacy were not demonstrated by these experiments.

Regional percentages are not transcribed here because some cortex/thalamus values in the text do not match the Figure 3 panel labels. The original panels are shown with their published labels.

P3B literature Figure 3: Cas9 reporter editing in Ai9 mice; regional fluorescence and cell-type quantification. — **Figure 3.** Cas9 reporter editing in Ai9 mice; regional fluorescence and cell-type quantification. Dong et al., Materials Today 92 (2026), 140–150. Reproduced without modification under CC BY 4.0. Source article.

P3B literature Figure 4: Adenine base editing in LumA mice; reporter imaging and target-site sequencing. — **Figure 4.** Adenine base editing in LumA mice; reporter imaging and target-site sequencing. Dong et al., Materials Today 92 (2026), 140–150. Reproduced without modification under CC BY 4.0. Source article.

Acute tolerability

The study reported a weaker inflammatory-marker response with P3B than with MC3. Plasma ALT and AST did not show significant between-group changes at the measured 6- and 24-hour endpoints. Histology at 6 hours did not show obvious tissue injury in the examined organs (Figure 5; n=3).

This is short-term preclinical evidence. The authors identify the 24-hour safety observation window as a limitation; long-term and repeated-dose safety remain to be established. The text and Figure 5 caption also differ in the stated sample compartment for inflammatory-marker profiling, so no tissue-specific cytokine claim is assigned here.

P3B literature Figure 5: Inflammatory markers, plasma liver enzymes and short-term organ histology. — **Figure 5.** Inflammatory markers, plasma liver enzymes and short-term organ histology. Dong et al., Materials Today 92 (2026), 140–150. Reproduced without modification under CC BY 4.0. Source article.

Reference and evidence basis

Dong S, Healy L, Gong F, et al. Biodegradable lipid nanoparticles for genome editing in the brain via intrathecal administration. Materials Today. 2026;92:140–150. doi:10.1016/j.mattod.2025.11.032.

Read the full paper · PubMed record

Structure identity: Figure 1f, P3B / H8TA2TB5. Formula and molecular weight were calculated from that structure; the newly formed stereocenter is unspecified. Main text and Figures 1–5 were reviewed. Supplementary files were not independently verified in this release.