DCL0022 · Research use only

FS01 · Formulation & Performance

FS01 · DCL0022 · Literature evidence

Intra-articular mRNA delivery and arthritis research

FS01 was selected for this local-delivery application. The study does not establish a universally best ionizable lipid.

Formulation and component weights

Component	Catalog	Molecular weight	Molar proportion	Mass %
FS01	DCL0022	866.33	50%	62.00%
DSPC	DC57005	790.15	10%	11.31%
Cholesterol	DCD-041	386.65	38.5%	21.31%
DMG-PEG2000	DC40169	2507	1.5%	5.38%

Source discrepancy: the Results paragraph reverses the names DSPC and cholesterol. This table follows the Materials and Methods assignment (FS01:DSPC:cholesterol:DMG-PEG2000 = 50:10:38.5:1.5), also supported by patent paragraph 0121. Confirm the intended composition against the final publication before experimental use.

Parameter	Reported information
N/P ratio	Not reported in the supplied main paper.
Therapeutic cargo	IL-1Ra mRNA; ANL3 mRNA; or their combination at a 1:1 mRNA mass ratio.
Mixing description	The Methods report microfluidic mixing and an organic:aqueous volume ratio of 3:1. The phase orientation requires confirmation; it has not been silently reversed.
Formulation context	The same lipid component ratio is described for the four-lipid screen and the FS01 therapeutic formulations.
FS01 screening particle size	Approximately 67 nm (main Results). Separate therapeutic formulation measurements are listed below.

Editable component mass calculator

Calculate masses from total lipid amount. Default values follow the Methods composition; calculated values are not experimental measurements.

Total lipid amount (µmol)

Component	MW	Molar ratio	Calculated mass (mg)
FS01			0.433165
DSPC			0.079015
Cholesterol			0.148860
DMG-PEG2000			0.037605

DMG-PEG2000 MW: 2507. Component mass (mg) = total µmol × normalized molar fraction × MW / 1000.

Measured therapeutic formulation properties

Parameter	IL-1Ra mRNA	ANL3 mRNA	IL-1Ra + ANL3 mRNA
Particle size (nm)	65.44 ± 0.32	66.55 ± 0.88	69.00 ± 1.71
PDI	0.12 ± 0.02	0.14 ± 0.01	0.137 ± 0.01
Zeta potential (mV)	8.16 ± 3.99	2.75 ± 5.23	−1.94 ± 1.76
Encapsulation efficiency (%)	96.33 ± 0.75	94.60 ± 1.34	96.33 ± 0.75

Transcribed from main Figure 2C. Reported ± values are preserved; this table does not infer an SD/SEM definition not specified in that panel.

Cell and animal performance

Study	Model / cargo	Finding	Interpretation and source
Lead-lipid comparison	Male C57BL/6 mice; intra-articular Fluc mRNA; n=4/group	FS01 had higher local luciferase expression and AUC than Lipid 5, SM-102 and LP01.	Matched 5 µg mRNA comparison; 6–48 h observation. No numerical fold advantage is inferred from the graph. Fig. 1F–G; Methods.
Joint tissue delivery	IL-1Ra mRNA; joint sections collected at 24 h	Greater IL-1Ra staining in synovium, meniscus and cartilage than the SM-102 formulation.	Local injection study, not evidence of systemic joint targeting. Fig. 1H.
Collagen-induced arthritis	DBA/1J mice; n=6/group; gait analysis n=5/group	Combined IL-1Ra/ANL3 formulation reduced joint inflammation and preserved cartilage; histology, micro-CT and gait were evaluated.	Single-cargo groups received 2 µg; combination received 4 µg total. Total mRNA dose was not matched, so this is not an isolated demonstration of equal-dose synergy. Fig. 2.
Inflammation and cartilage markers	CIA joint tissue and immune readouts	Reported reductions in inflammatory and matrix-degrading markers, with preservation of cartilage-associated readouts.	Complete payload-loaded formulation; do not attribute the effect to FS01 alone. Figs. 3–4.
Spontaneous rheumatoid arthritis	TNF-transgenic mice; 5–6/group according to treatment arm	Combination therapy improved reported joint pathology and cartilage-associated outcomes.	Preclinical model; monotherapy and combination groups again used different total mRNA amounts. Fig. 5.
Surgical osteoarthritis	Early- and late-stage DMM mouse models; n=5/group	Improved cartilage histology and Mankin/OARSI scores; ADAMTS5, MMP-13 and collagen II were examined.	Combination formulation; 4 µg total mRNA per injection. Fig. 6.
Cell and animal tolerability	SW1353 / ATDC5 cells, 24 h; treated OA and TNF-Tg mice	Cell viability, body weight, serum chemistry and organ histology were assessed; the authors reported a favorable preliminary tolerability profile.	Study-specific observations do not establish clinical safety or long-term safety. Fig. 7.

Evidence boundary: mouse and cell studies; no human efficacy established. The supplied file is a journal pre-proof. Supplementary figures and underlying raw data were not supplied for independent verification. No synthesis procedures, NMR spectra or chemical analytical data are reproduced.

Original study figures

Wang et al. 2026 Figure 1: Lipid screening, local luciferase expression and joint tissue delivery. — **Original Figure 1.** Lipid screening, local luciferase expression and joint tissue delivery. Source: Wang et al., Molecular Therapy (2026), DOI 10.1016/j.ymthe.2026.10.021, journal pre-proof. Original panel labels and source watermarks retained. Click to enlarge.

Wang et al. 2026 Figure 2: mRNA expression, formulation properties, CIA pathology and gait measurements. — **Original Figure 2.** mRNA expression, formulation properties, CIA pathology and gait measurements. Source: Wang et al., Molecular Therapy (2026), DOI 10.1016/j.ymthe.2026.10.021, journal pre-proof. Original panel labels and source watermarks retained. Click to enlarge.

Wang et al. 2026 Figure 6: Cartilage histology and immunohistochemistry in early- and late-stage surgical osteoarthritis. — **Original Figure 6.** Cartilage histology and immunohistochemistry in early- and late-stage surgical osteoarthritis. Source: Wang et al., Molecular Therapy (2026), DOI 10.1016/j.ymthe.2026.10.021, journal pre-proof. Original panel labels and source watermarks retained. Click to enlarge.

Wang et al. 2026 Figure 7: Cell viability and preliminary animal tolerability assessments. — **Original Figure 7.** Cell viability and preliminary animal tolerability assessments. Source: Wang et al., Molecular Therapy (2026), DOI 10.1016/j.ymthe.2026.10.021, journal pre-proof. Original panel labels and source watermarks retained. Click to enlarge.

References

Wang G, et al. A Combinatorial mRNA Therapy for Treating Rheumatoid Arthritis and Osteoarthritis by Inhibiting Inflammation and Preventing Cartilage Degeneration. Molecular Therapy (2026), journal pre-proof. DOI: 10.1016/j.ymthe.2026.10.021. Main source for the study tables and figures on this page.
Guo K, et al. A novel ionizable lipid with comprehensive improvements in transfection potency, immune profile and safety of lipid nanoparticle. Journal of Controlled Release 386, 114126 (2025). DOI: 10.1016/j.jconrel.2025.114126. Earlier FS01 publication cited by Wang et al.; not used to fill missing N/P values.
CN120208802A, published 27 June 2025. FS01 structure: paragraphs 0116–0119, PDF page 14; formulation component order: paragraph 0121. Chemical preparation details are not reproduced here.