ALC-0307

Literature evidence · DC67546

Formulation & Performance

The 2021 CD4-targeting study supplies direct formulation and biological evidence. Its antibody-conjugated research particles and the later k-abe clinical formulation are separate records.

Tombácz et al. explicitly identify ALC-0307 as the default ionizable lipid. The platform developer’s official 16 May 2025 announcement separately names ALC-0307 and ALC-0159 in the k-abe program. The latter connection is based on a corporate primary source rather than a named-lipid statement in the clinical paper.

Formulation components and molecular-weight conversion

Component	DC Chemicals product	Molecular weight	Molar ratio	Mass at 1 µmol total lipid (mg)
ALC-0307	DC67546	863.5	50	Not calculable from disclosed data
Phosphatidylcholine (specific species not resolved)	Not uniquely mapped	Not established	10	Not calculable from disclosed data
Cholesterol	DCD-041	386.65	38.5	Not calculable from disclosed data
PEG lipid (specific identity not resolved)	Not uniquely mapped	Not established	1.5	Not calculable from disclosed data

Tombácz 2021 core ratio: 50:10:38.5:1.5 mol/mol. RNA:total lipid approximately 0.04:1 by mass, equivalent to approximately 1:25. CD4-targeted particles also have antibody functionalization; this core ratio is not a complete conjugated-particle recipe. Do not substitute DSPC, ALC-0159 or DMG-PEG2000 for the generic components without confirming identity. These are not verified k-abe clinical ratios.

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 %
ALC-0307	—	—
Phosphatidylcholine (specific species not resolved)	—	—
Cholesterol	—	—
PEG lipid (specific identity not resolved)	—	—

Particle characterization

Particle	Reported result	Source
Unconjugated LNP	Approximately 80 nm	Materials and methods: Characterization of LNPs
Antibody-conjugated LNP	88.37 ± 4.2 nm; PDI 0.1	Materials and methods: Characterization of LNPs

Values describe the published research formulation, not specifications for free ALC-0307.

Cell-based evidence

System	Observation	Source
Human donor CD4+ T cells	Selective binding and dose-responsive luciferase expression relative to isotype-IgG LNP controls	Figure 1
Ai6 mouse splenocytes	Approximately 80% reporter-positive cells in the CD3+CD8− gate with targeted Cre mRNA-LNPs	Figure 2; CD4 staining was transiently reduced after targeting, hence the alternative gate

Animal delivery and reporter activity

Readout	Finding	Study boundary
Cre/loxP reporter recombination	Roughly 60% reporter-positive CD4+ cells in spleen and 40% in lymph nodes	Figure 5, 24-hour mouse endpoint; dose-response groups n=8–9; not CAR-T generation or antitumor response
Luciferase in isolated splenic CD3+ cells	33-fold greater signal with anti-CD4 targeting than isotype-IgG controls	Figure 4D, 5-hour endpoint, n=3
High-dose limitation	The 90 μg RNA dose was toxic in all LNP groups and was excluded from subsequent experiments	Results preceding Figure 5; do not describe the platform as universally nontoxic

CD4 specificity belongs to the antibody-conjugated formulation, not the free lipid molecule.

Separate k-abe clinical-program evidence

Evidence	Finding	Source and boundary
Lipid identity	ALC-0307 and ALC-0159 explicitly named	Acuitas official release, May 16, 2025, PDF p2; corporate primary identity confirmation
Initial clinical report	One infant, two administrations and seven weeks of early follow-up; increased dietary protein tolerance and reduced nitrogen-scavenger requirement	Musunuru 2025 NEJM, Summary and Clinical Course
Clinical tolerability	Transient aminotransferase elevations; no serious adverse events in the initial short report	Single-patient evidence; not general lipid safety
Monkey preclinical assessment	Transient ALT/AST elevations; plasma lipid excipient concentrations >99.5% below peak by two weeks	NEJM Preclinical Validation; plasma decline is not complete whole-body clearance

The clinical paper does not name ALC-0307; the explicit platform-developer announcement supplies that identity connection. The release mentions three administrations, whereas the initial paper covers two. Keep their reporting cutoffs distinct.

Original study figures

CD4-targeted biological results, Figures 1–7 — Original source figures.