GalNAc Lipid GL6 (GalNAc Lipid 1004)

Literature evidence · DC60502

Formulation & Performance

Hepatic targeting evidence from the 2023 Nature Communications paper and its complete supporting information.

The paper identifies GL6 as a lysine-scaffold GalNAc ligand with a PEG spacer and a DSG lipid anchor. GalNAc Lipid 1004 is retained as the catalog alias. Commercial molecular-weight and formula values are catalog specifications; the paper describes an average PEG spacer length.

Formulation components and molecular-weight conversion

Component	DC Chemicals product	Molecular weight	Molar ratio	Mass at 1 µmol total lipid (mg)
Undisclosed ionizable amino lipid	Not uniquely mapped	Not established	55	Not calculable from disclosed data
Cholesterol	DCD-041	386.65	38.15	0.147507
DSPC	DC57005	790.15	4.7	0.037137
PEG-lipid, exact identity undisclosed	Not uniquely mapped	Not established	2.1	Not calculable from disclosed data
GalNAc Lipid GL6	DC60502	3449.38	0.05	0.001725

Methods give the four-base-lipid molar percentages for some mouse studies; the listed 0.05% GL6 condition completes a nominal 100%. These values are not assumed to define every mouse batch or the NHP formulation. The NHP table confirms 0.05% GL6 but does not disclose the full composition. Exact amino-lipid and PEG-lipid MWs are unavailable.

Component mass calculator

Not all inputs are assigned to a single verified study formulation; unassigned fields are 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 %
Undisclosed ionizable amino lipid	—	—
Cholesterol	—	—
DSPC	—	—
PEG-lipid, exact identity undisclosed	—	—
GalNAc Lipid GL6	—	—

Mouse formulation characterization

Table S1 entry / figure	Cargo target	GL6 mol%	Size nm	PDI	RNA entrapment %
1 / 1d	Angptl3	0.05	98.61	0.013	94.91
3 / 1e	Pcsk9; post-insertion	0.5	79.3	0.072	94.7
6 / 1f,g	Angptl3	0.05	100.4	0.034	93.59
11 / 2b	Angptl3	0.05	98.61	0.013	94.91
16 / 2c	Angptl3	0.05	66.73	0.018	98.36
17 / 2d	Angptl3	0.05	77.24	0.028	99.2

SI Table S1, p. 1. These are separate preparations; entry 3 uses post-insertion. Do not merge their particle values.

Primate formulation characterization

Table S2 entry	GL6 mol%	Size nm	PDI	RNA entrapment %	RNA dose
1	0	74.97	0.057	92.6	2 mg/kg
2	0	72.73	0.032	94.3	2 mg/kg
3	0.05	72.93	0.083	93.6	2 mg/kg
4	0.05	71.97	0.042	93.3	2 mg/kg

SI Table S2, p. 2; two standard and two GL6-containing preparations. No N/P or undisclosed amino-lipid identity is inferred.

Mouse efficacy: matched comparisons

Comparison	Outcome	Model / source
GL6 vs GL3	Mean Angptl3 editing 31% vs 23%; p=0.0086.	Ldlr-null mice, 0.1 mg/kg; n=5/group; Fig. 1d.
GL6 vs GL3	Mean Pcsk9 editing 43% vs 33%; p=0.01.	Ldlr-null mice, 0.25 mg/kg; n=5/group; Fig. 1e.
GL6 vs shorter-spacer GL5	Mean Angptl3 editing 56% vs 18%; p<0.0001.	Ldlr-null mice, 0.3 mg/kg; n=4-5/group; Fig. 1f.
Addition of 0.05% GL6	Editing increased from 9% to 39% in Ldlr-null mice; p<0.0001.	0.25 mg/kg; Fig. 2c. Comparable delivery was retained in WT and heterozygous animals.

Liver editing was assessed 5-10 days after dosing. Values are reported study means, not a customer performance specification.

Nonhuman-primate efficacy and durability

Endpoint	Result	Context
Liver ANGPTL3 editing	Mean 61% with GalNAc-LNPs vs 5% with standard LNPs.	Somatic LDLR-deficient cynomolgus monkeys, 2 mg/kg RNA; six GL6-treated animals across studies; Fig. 3e.
ANGPTL3 protein	89% reduction in the LDLR-deficient model.	Fig. 3f; distinct from percentage liver DNA editing.
LDL cholesterol	Approximately 35% reduction, about 100 mg/dL, maintained for three months.	LDLR-deficient model; Fig. 3g.
Longer follow-up	Sustained ANGPTL3 protein reduction assessed through six months.	Wild-type monkeys; Fig. 3h. This does not establish six-month persistence of lipid or RNA.
Extrahepatic editing	Low editing in the assessed non-liver tissues.	Fig. 4; tissue sampling and limits of the study apply.

Tolerability and study limits

Group	Reported observations	Boundary
LDLR-deficient NHPs	Maximal mean ALT 480 U/L at 48 h; AST 537 U/L at 6 h; both returned to baseline by day 14.	Main text and SI Fig. S5; AST was not significantly different from vehicle in the cited comparison.
Wild-type NHPs	Maximal mean ALT 710 U/L at 48 h; AST 650 U/L at 6 h; both normalized by day 14.	Transient TNF-alpha and MCP-1 increases peaked at 24 h and returned toward baseline within 7 days.
Interpretation	Authors describe tolerability with transient biochemical/cytokine changes.	Animals received premedication. The findings are not evidence of no toxicity or clinical safety.

Original study figures

Figure 2: Mouse hepatic editing

Figure 3: Primate editing and durability

Figure 4: Tissue editing distribution