The microfluidic method uses ethanol-solubilized lipids and pH-4 citrate RNA, aqueous:ethanol 3:1 v/v, and 12 mL/min total flow. The 10:1 mass ratio is explicitly tied to initial lipid:mRNA screening. No N/P ratio or separate selected-formulation ionizable-lipid:total-editing-RNA ratio is given.
Main methods are reported laboratory conditions, not a validated product-specific manufacturing specification. · Main PDF pp.12–13sales@dcchemicals.com
BIP-20
Formulation & Performance
Literature-reported formulation composition
| Component | mol% | Role |
|---|---|---|
| BiP-20 | 50 | Ionizable lipid |
| DOPE | 10 | Helper phospholipid |
| Cholesterol | 38.5 | Sterol |
| DMPE-PEG2000 | 1.5 | PEG lipid |
| Reported total | 100 | Source values retained |
Formulation calculator unavailable. The study identifies DMPE-PEG2000 (C14-PEG2K), but does not give an exact average molecular weight or supplier catalog. Confirm that material before calculating masses. Do not silently substitute DMG-PEG2000. Obtain and verify the complete composition and component molecular weights before planning component quantities.
Literature-reported performance for the cited formulation
Literature-reported5.9-fold vs MC3CD1; 3 µg FLuc mRNA IV; 4 h comparison, with 24 h also assessed; n=3 · Similar expression to SM102; not a claim of superiority over SM102Main Fig.1f, PDF p.3; text p.4
Literature-reported~64% indels10 µg total Cas9 mRNA + sgTTR (1:1 w/w), IV; CD1 mice; day 7; n=4 · LP01 required ~30 µg total RNA for a comparable editing levelMain Fig.1h and text, PDF pp.3–4
Literature-reported~20% indels2 µg total Cas9 mRNA + sgTTR, IV; CD1; day 7; n=4 · Separate from the 10 µg condition and 1 µg SI experimentMain Fig.1h and text, PDF pp.3–4
Literature-reported4.30% TTAC insertionCD1; reported 50 µg RNA/mouse, IV; day 7; n=4; see dose wording note · SM102 3.33%; MC3 1.33%; LP01 0.1225%; significance reported vs MC3 and LP01Main Fig.1j and text, PDF pp.3–4; SI Fig.S8, PDF p.10
Literature-reported6.56TNS titration, n=4; fit shown as 6.561; measured before composition optimization in the report · Formulation-dependent value; exact molar composition for this titration is not separately restatedMain Fig.1e, PDF p.3; text p.4; TNS method p.12
Literature-reported~8% at 30 min; ~6% at 1 h5 µg modified DNA barcode IV; LysoTag mice; n=4 · Non-lysosomal flow-through / (flow-through + lysosomal) barcode reads; not an mRNA transfection percentageMain Fig.2j, PDF p.5; caption p.6; explanation p.7
Three reported BiP-20 formulations
| Purpose | BiP-20 / DOPE / cholesterol / DMPE-PEG2000 (mol%) | Interpretation |
|---|---|---|
| Selected for subsequent studies | 50 / 10 / 38.5 / 1.5 | BiP20-R; selected because the higher-mean BiP-20-19 group was more variable. |
| Initial lipid screening | 35 / 16 / 46.5 / 2.5 | 10:1 ionizable lipid:mRNA w/w explicitly reported for screening. |
| Highest mean in formulation screen | 45 / 16 / 38.5 / 0.5 | BiP-20-19: 1.72-fold vs BiP20-R at 4 h, n=3, p=0.0216. |
Main PDF pp.2–4,12; SI Fig.S5e, PDF p.7. Component order is kept identical across rows.
Helper-lipid comparison before composition optimization
| Helper lipid | DLS diameter (nm) | PDI | mRNA EE (%) | Reporter result |
|---|---|---|---|---|
| DOPE | ~42 | ~0.14 | ~98 | Stronger liver expression; n=3 mice |
| DSPC | ~40 | ~0.17 | ~98 | Lower reporter expression; n=2 mice |
SI Fig.S4, PDF p.6 (printed p.5). Diameter, PDI and EE are approximate visual readings of plotted means, not tabulated values. These are helper-comparison LNPs; do not transfer these properties to the final BiP20-R editing formulation. Fig.S4 does not restate full composition.
Mouse gene-editing outcomes
| Cargo / endpoint | Dose and readout | BiP-20 result | Benchmark / interpretation |
|---|---|---|---|
| Cas9 + sgTTR / genomic indels | 2 µg total RNA; day 7; n=4 | ~20% | Genomic sequencing; separate from serum TTR protein |
| Cas9 + sgTTR / genomic indels | 10 µg total RNA; day 7; n=4 | ~64% | LP01 ~30 µg for a comparable editing level |
| Cas9 + sgTTR / serum TTR | 1 µg total RNA; day 7; n=4 | ~50% reduction; p=0.0093 | SI reports up to 40% indels; not a mean editing percentage |
| PEmax + pegRNA + ngRNA / TTAC insertion | Reported 50 µg/mouse; day 7; n=4 | 4.30% | SM102 3.33%; MC3 1.33%; LP01 0.1225% |
Main Fig.1h–j and text, PDF pp.3–4; SI Figs.S7–S8, PDF pp.9–10. Prime-editing significance was established vs MC3 and LP01, not vs SM102. Main p.4 calls the 50 µg dose both total RNA and “total mRNA”; obtain clarification before reproducing component masses.
Additional reported findings
LysoBC yielded approximately 8% at 30 min and 6% at 1 h. It compares DNA barcode reads in non-HA-bound flow-through against flow-through plus isolated HA-tagged endolysosomal reads. The authors treat this as a proxy for extra-lysosomal localization; it does not prove that every counted barcode supports productive delivery.
5 µg modified DNA barcode, IV; LysoTag mice; n=4. Cargo and assay differ from mRNA expression and editing studies. · Main Fig.2j, PDF pp.5–6; qualification p.7; SI Fig.S10, PDF p.12ApoE knockout nearly eliminated liver reporter signal, while LDL-R knockout substantially reduced it. These experiments support ApoE-dependent uptake with a contribution from LDL-R and potentially other receptors.
C57BL/6, ApoE−/− and LDL-R−/− cohorts, n=3; reporter expression at 4 h and 24 h. This is an uptake-dependence result, not a measured receptor-specific endosomal escape rate. · Main PDF p.4; SI Fig.S6, PDF p.8At 50 µg total RNA per mouse and 24 h after IV retro-orbital administration, ALT and AST were comparable to untreated controls. BiP-20 did not significantly increase IL-6; TNFα was below the assay detection limit.
Single-dose serum endpoints only. ALT/AST n=4; IL-6 treated groups n=4, untreated n=3. No claim of clinical, repeat-dose or long-term safety. · Main Safety profile, PDF p.7; SI Fig.S11, PDF p.13The SI identifies BiP-20 as O,O-bis(2-octyldodecyl)-N-(2-(dimethylamino)ethyl)phosphoramidate, formula C44H93N2O3P, MW 729.21 g/mol. It has two saturated branched C20 tails and a dimethylaminoethyl head attached through a phosphoramidate N–H.
Identity is consistent with the existing DC68021 SMILES and formula; product specifications are retained. The SI reports synthesis and characterization, not a DC Chemicals batch COA. · Main Fig.1c, PDF p.3; SI PDF p.51 (printed p.50); BiP-20 NMR/HRMS SI PDF pp.137–139Literature Data DisclaimerAll formulation parameters and performance values shown in this section are derived from the cited publication and are provided for reference only. These results were obtained using the specific materials, formulation process, cargo, dose, analytical method, model and administration route described in that study. Unless otherwise stated, the data were not generated or independently verified by DC Chemicals. DC Chemicals supplies the lipid compound only and does not guarantee that customers will reproduce the reported LNP properties or biological performance.
The administration route shown above was used in the cited study and is not a clinical-use instruction or recommendation by DC Chemicals.
The administration route shown above was used in the cited study and is not a clinical-use instruction or recommendation by DC Chemicals.
Cited literature for this formulation and performance datasetJozić A, Le Roux C, Kim J, et al. In vivo endosomal escape assay identifies mechanisms for efficient hepatic LNP delivery. Nature Biotechnology. Published online March 11, 2026. doi:10.1038/s41587-026-03022-6. DOI: 10.1038/s41587-026-03022-6
Primary article and 215-page SI reviewed for BiP-20. Exact composition and reported endpoints are separated from visual estimates and from the initial LiP/BiP library. Additional supplementary Excel data were not supplied.
Primary article and 215-page SI reviewed for BiP-20. Exact composition and reported endpoints are separated from visual estimates and from the initial LiP/BiP library. Additional supplementary Excel data were not supplied.