SM-86 (Lipid 5)

Literature evidence · DC31024

Formulation & Performance

Three enzyme-replacement mRNA programs · Liver expression and disease biomarkers · Separate formulation and dose records

The publication explicitly identifies SM-86 but does not disclose its chemical structure. The existing catalog structure and Lipid 5 alias are retained; the paper is not a verification of the supplied commercial batch.

Formulation components and molecular-weight conversion

Component	DC Chemicals product	Molecular weight	Molar ratio	Mass at 1 µmol total lipid (mg)
SM-86	DC31024	710.165	Not disclosed	Not calculable from disclosed data
DSPC	DC57005	790.15	Not disclosed	Not calculable from disclosed data
Cholesterol	DCD-041	386.65	Not disclosed	Not calculable from disclosed data
OL-56 (PEG-lipid)	Not uniquely mapped	Not established	Not disclosed	Not calculable from disclosed data

The four components are explicitly named, but their molar proportions, N/P ratio and lipid:RNA mass ratio are not disclosed. OL-56 cannot be replaced by DMG-PEG2000 when describing this study. Supplementary Table 9 separately lists SM-86/OL-56 and SM-86/DMG formulations; these records are not merged.

Component mass calculator

The source does not disclose all inputs; missing fields are intentionally blank. Enter your own values to calculate a research scenario. Molecular weights and ratios are editable. Results are calculated, not measured study data. No N/P or RNA dose is inferred.

Total lipid (µmol)

Component	Mass (mg)	Mass %
SM-86	—	—
DSPC	—	—
Cholesterol	—	—
OL-56 (PEG-lipid)	—	—

Three formulations, three distinct cargos

Program / indication	RNA cargo	Diameter	PDI	Encapsulation
mRNA-3927 / propionic acidemia	hPCCA + hPCCB, 1:1 RNA molar ratio	70 nm	0.14	>96%
mRNA-3705 / methylmalonic acidemia	hMUT	71 nm	0.07	97%
mRNA-3210 / phenylketonuria	hPAH	77 nm	0.13	95%

Source: main article, Methods, mRNA synthesis and formulation, PDF p. 8. Particle values belong to the corresponding complete formulation.

Formulation context

Parameter	Reported value
Preparation platform	Microfluidic mixing of ethanolic lipids with aqueous mRNA
Aqueous:ethanol volume ratio	3:1
Aqueous buffer	25 mM sodium acetate, pH 5
Final dispersion	20 mM Tris, pH 7.5; 8% sucrose; 1 mM DTPA
Total flow rate / N/P / lipid:RNA mass ratio	Not disclosed
Component molar percentages / OL-56 molecular weight	Not disclosed

Source: Methods, PDF p. 8. Reported formulation context, not a validated manufacturing instruction for the commercial lipid.

Propionic acidemia: sustained biomarker response

Study element	Evidence
Model	Pcca−/−(A138T) mice
Treatment	mRNA-3927, 0.5 mg total RNA/kg IV on days 0 and 28
Biomarkers	Plasma 2-methylcitrate, 3-hydroxypropionate and C3/C2 ratio
Response	Biomarker reduction lasted approximately 3–4 weeks after the first dose; repeat treatment produced another response
Replicates	n = 6 per group in the pharmacodynamic experiment
Negative result	Liver PCC activity increased numerically, but the reported comparison was not statistically significant

Source: Figure 2 and Supplementary Table 2. The 1 and 2 mg/kg single-dose pharmacokinetic experiments are separate from this 0.5 mg/kg pharmacodynamic study.

Methylmalonic acidemia: protein and enzyme activity

24-hour endpoint	Control (n=4)	0.2 mg RNA/kg IV (n=5)	0.5 mg RNA/kg IV (n=4)
Liver hMUT protein (ng/mg protein)	0.0 ± 0.0	45.0 ± 42.2; p=0.0836	70.4 ± 24.2; p=0.0136
Liver MUT activity (nmol/min/mg protein)	2.8 ± 0.2	5.7 ± 2.8; p=0.4577	10.7 ± 6.5; p=0.0317
Plasma MMA, baseline → day 1 (µM)	892 ± 241 → 1260 ± 280	614 ± 190 → 425 ± 422	589 ± 206 → 114 ± 20

Mut−/−;TgINS-CBA-G715V mice; mean ± SD. Protein and activity p values compare with control. The high-dose within-group plasma comparison has p=0.0201; the paper reports a 78 ± 3.2% reduction from baseline. One partially dosed high-dose animal was excluded. Source: Figure 3 and Supplementary Table 4, SI p. 5.

Methylmalonic acidemia: tissue biomarker response

Tissue MMA at 24 h (nmol/g)	Control	0.5 mg RNA/kg IV	p versus control
Liver	4662.5 ± 1752.2	7.9 ± 15.8	0.0011
Kidney	3480.0 ± 1612.1	189.7 ± 128.9	0.0052

Mean ± SD; n=4 per displayed group. Tissue metabolite reduction does not itself demonstrate mRNA transfection of those tissues. Source: Supplementary Table 4.

Phenylketonuria: hepatic expression and blood phenylalanine

Single IV dose (mg RNA/kg)	Peak liver hPAH (ng/g)	Time of protein peak	Minimum blood Phe (µM)
0.25	6950	24 h	1105 ± 209
0.5	16,700	24 h	561 ± 279
1.0	35,600	8 h	138 ± 78

PAHenu2 mice. Phe mean ± SD, n=8 per group; protein sampling group sizes vary by time point (Figure 4). Blood Phe returned toward baseline by 168 h. The low-dose minimum is 1105 in Supplementary Table 7 and 1110 in the main text; this table follows the SI. Source: Figure 4 and Supplementary Table 7, SI p. 8.

Tolerability and interpretation

Evidence	Scope
Reported rat NOAEL	mRNA-3927: 3 mg/kg; mRNA-3705: 5 mg/kg; mRNA-3210: 3 mg/kg
What the values describe	Study-program-specific complete RNA-LNP formulations in Sprague–Dawley rats (main Table 1), not standalone SM-86 toxicity
Nonhuman-primate records	The SI inventories cynomolgus pharmacokinetic studies. An inventory entry is not evidence of therapeutic efficacy in monkeys
Cell data	No product-specific cell transfection ranking is assigned from this predominantly in vivo PK/PD study
Human relevance	Translational dose modeling is a prediction, not observed human efficacy or a human safety guarantee

Source: main Table 1 and Supplementary Tables 8–10. Full study-specific toxicology outcomes are not reproduced in this publication.

Original study figures

Figure 2: mRNA-3927 in the PA mouse model

Figure 3: mRNA-3705 in the MMA mouse model

Figure 4: mRNA-3210 in the PKU mouse model