Safer and efficient base editing and prime editing via ribonucleoproteins delivered through optimized lipid-nanoparticle formulations
Data files
Dec 02, 2025 version files 10.16 GB
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EDFig1.zip
534.48 MB
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EDFig2.zip
201.69 MB
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EDFig3.zip
2.43 GB
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EDFig4.zip
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Fig_4_5_uncropped_gels.pdf
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Fig1.zip
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Fig2.zip
854.89 MB
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Fig3.zip
500.51 MB
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Fig4.zip
792.45 MB
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Fig5.zip
318.80 MB
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Fig6.zip
54.29 MB
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README.md
22.51 KB
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Sequencing.zip
3.49 GB
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Supplementary_Figure_1.zip
88.92 KB
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Supplementary_Figure_2.zip
732.86 MB
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Supplementary_Figure_3.zip
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Supplementary_Figure_4.zip
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Supplementary_Figure_6.zip
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Supplementary_Figure_7.zip
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Supplementary_Figure_8.zip
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Abstract
Delivering ribonucleoproteins (RNPs) for in vivo genome editing is safer than using viruses encoding for Cas9 and its respective guide RNA. However, transient RNP activity does not typically lead to optimal editing outcomes. Here, we show that the efficiency of delivering RNPs can be enhanced by cell-penetrating peptides (covalently fused to the protein or as excipients) and that lipid nanoparticles (LNPs) encapsulating RNPs can be optimized for enhanced RNP stability, delivery efficiency, and editing potency. Specifically, after screening for suitable ionizable cationic lipids and by optimizing the concentration of the synthetic lipid DMG-PEG 2000, we show that the encapsulation, via microfluidic mixing, of adenine base editor and prime editor RNPs within LNPs using the ionizable lipid SM102 can result in in vivo editing-efficiency enhancements larger than 300-fold (with respect to the delivery of the naked RNP) without detectable off-target edits. We believe that chemically defined LNP formulations optimized for RNP-encapsulation stability and delivery efficiency will lead to safer genome editing.
Data collection of raw sequencing files, raw imaging files, and other data associated with the corresponding publication.
Description of the data and file structure
- The data are matched to figures and panels of the corresponding publication and sorted in the subdirectories. Below, X denotes a figure number.
- Fig X uncropped gels.pdf contain uncropped gels matched to Figure X, with appropriate panels assigned within the pdf file.
- FigX.csv contain numerical values used to prepare graphs, and the results of statistic tests as reported by GraphPad Prism 10 software.
- FigX_FC subdirectories contain flow cytometry data with events exported in .csv format and reports in .pdf format.
- FigX_FC_key.csv files contain a legend matching flow cytometry results to samples reported in the figures.
- Sequencing directory contains raw sequencing reads as deposited in NCBI Sequencing Read Archive and SraRunTable.csv file that contains the associated metadata.
- Software requirements: PDF: Adobe Acrobat Reader or equivalent; CSV: Microsoft Notepad, Microsoft Excel is recommended; PNG, TIF, EMF: Microsoft Paint or equivalent; MP4: Microsoft Media Player or equivalent.
Fig1.zip
Fig1.csv
Fig 1 b,c,f,g:
- Volume (ml), Vol (ml), volume (CV): Elution volume, X-axis. CV = column volumes.
- A260 (mAU): Absorbance at 260 nm, left Y-axis, dotted line.
- A280 (mAU): Absorbance at 280 nm, left Y-axis, solid line.
- Imidazole (mM): Concentration of imidazole in eluent in mmol/L, right Y-axis, dashed line.
Fig 1 e:
- UV1 (260 nm)_volume_CV: Elution volume, X-axis, values for left Y-axis.
- UV1 (260 nm)_mAU: Absorbance at 260 nm, left Y-axis, dotted line.
- UV2 (280 nm)_mAU: Absorbance at 280 nm, left Y-axis, solid line.
- Imidazole_volume_CV: Elution volume, X-axis, values for right Y-axis.
- Imidazole (mM): Concentration of imidazole in eluent in mmol/L, right Y-axis, dashed line.
Fig 1 j:
- Wavelength (nm): X-axis
- ABE8e TALON: Y-axis, normalized absorbance value for adenine base editor 8e protein (ABE8e) collected from TALON chromatography, black line.
- ABE 1D4: Y-axis, normalized absorbance value for ABE8e collected from 1D4 chromatography, red line.
- ABE SEC aggregate: Y-axis, normalized absorbance value for ABE8e aggregate collected from size exclusion chromatography (SEC), green line.
- ABE SEC main peak: Y-axis, normalized absorbance value for ABE8e main peak collected from SEC, purple line.
Fig 1k:
- Elution volume (ml): X-axis, elution volume from SEC column.
- ABE8e, prime editor protein (PE2), SEC standards: Y-axis. Normalized absorbance at 280 nm of SEC eluates. ABE8e: solid black line; PE2, solid red line; SEC standards = solid grey line.
Fig 1l main:
- Temperature (degC): X-axis
- ABE1, ABE2, ABE3: Y-axis, FRET fluorescence intensity for ABE protein.
- ABE RNP NF 1, ABE RNP NF 2, ABE RNP NF 3: Y-axis, FRET fluorescence intensity for ABE ribonucleoprotein (RNP) with non-refolded single guide RNA (sgRNA).
- ABE RNP F1, ABE RNP F2, ABE RNP F3: Y-axis, FRET fluorescence intensity for ABE ribonucleoprotein (RNP) with refolded single guide RNA (sgRNA).
- Buffer1, Buffer2, Buffer3: Y-axis, FRET fluorescence intensity for buffer-only control.
Fig 1l insert:
- dF/dT (1/degC): negative gradient of the FRET fluorescence intensity in relation to the temperature
- ABE 1, ABE 2, ABE 3, ABE RNP NF 1, ABE RNP NF 2, ABE RNP NF 3, ABE RNP F 1, ABE RNP F 2, ABE RNP F 3, Buffer1, Buffer2, Buffer3: Y-axis, as in Fig 1l main.
Fig 1o main, Fig 1o insert: analogous as for Fig 1l with prime editor protein (PE2) complexed with engineered prime editing guide RNA (epegRNA, PE2 RNP).
Fig 1 uncropped gels.pdf - images of uncropped gels with outlined regions of interest.
Fig2.zip
Fig2b
Directories contain source microscopic images.
*.emf files contain the results of flow cytometry analysis. FITC-A = green fluorescence intensity; PE-A = red fluorescence intensity.
Fig2b-d_FC - raw fluorescence cytometry data.
- FSC-H: forward scatter, height.
- SSC-H: side scatter, height.
- FSC-A: forward scatter, area.
- SSC-A: side scatter, area.
- FITC-A: green (GFP) fluorescence intensity.
- Pacific Blue-A: Pacific blue (DAPI) fluorescence intensity.
- PE-A: red fluorescence intensity.
- Width: signal width.
- Time: peak time (milliseconds).
Fig2f
Analogous to Fig2b.
231001_1413_mTmG.csv: raw flow cytometry data.
- Specimen No.: specimen number.
- Specimen: specimen name.
- Plate ID: plate identifier.
- Well ID: well coordinate.
- Sample: sample name.
- Sample Notes (blank)
- Run time: date (mm/dd/yyyy) and time (hh:min) of the measurement.
- All Count: total number of events.
- All Abs Count: total events per second.
- P2 Count: number of events gated on gate P2.
- P1% Parent: percentage of total events gated through gate P1.
- P2% Parent: percentage of events from gate P1 gated through gate P2.
- P2 count: number of events gated through gate P2.
- Q3-1 % Parent: percentage of events from gate P2 in gate Q3-1 (RFP-positive (RFP+) GFP-negative (GFP-))
- Q3-2 % Parent: percentage of events from gate P2 in gate Q3-2 (RFP+ GFP+)
- Q3-3 % Parent: percentage of events from gate P2 in gate Q3-3 (RFP- GFP-)
- Q3-4 % Parent: percentage of events from gate P2 in gate Q3-4 (RFP- GFP+)
- M4 % Parent: percentage of events from gate P2 in gate M4 (DAPI-negative).
Fig2f-g_FC: raw flow cytometry data, analogous as in Fig2b-d_FC.
Fig2.csv: data used to prepare graphs in Fig2.
Fig2c
- Enzyme concentration (μM): X-axis, enzyme concentration in micromol/L.
- Cre, CPP5-Cre, Tat-Cre, ANTP-Cre, No enzyme: Y-axis, GFP to RFP conversion of HEK GFP RFP cells, individual biological replicates. Conversion = ratio of RFP-positive and sum of RFP-positive and GFP-positive gated events.
Fig2d
- Peptide concentration (μM): X-axis, 6xHis-CM18-PTD4 peptide concentration in micromol/L. Cre at 0.5 micromol/L.
- Cre, CPP5-Cre, Tat-Cre, ANTP-Cre, No enzyme: Y-axis, GFP to RFP conversion of HEK GFP RFP cells, individual biological replicates.
Fig2g
- Non-treated: tdTomato to eGFP conversion of of mT/mG fibroblasts, non-treated control. Conversion = ratio of eGFP-positive and sum of tdTomato-positive and eGFP-positive gated events.
- Other samples analogously: Cre, Cre protein; Cre + P, Cre protein with 6xHis-CM18-PTD4; CPP5-Cre, CPP5-Cre protein; TAT-Cre, TAT-cre protein; ANTP-Cre, ANTP-Cre protein; Cre + L3000, Cre complexed with Lipofectamine 3000.
Fig2i-p: two-photon fluorescence tomograms of Cre-treated mT/mG mice.
Fig3.zip
Fig3c: Microscope images and flow cytometry plots for ABE-treated rd12 reporter cells.
PE-A: fluorescence intensity of mCherry
FITC-A: fluorescence intensity of eGFP.
Q3-1: events that are mCherry-positive (mCherry+) eGFP-negative (eGFP-)
Q3-2: events that are mCherry+ eGFP+
Q3-3: events that are mCherry- eGFP-
Q3-4: events that are mCherry- eGFP+
Fig3c-d_FC: raw flow cytometry data.
Fig3.csv: data used to generate graphs.
Fig3b
- A6: A6 only, percentage of genes with adenines precisely edited in the position 6 of the protospacer.
- A6 + bystander: percentage of genes with adenines edited in the position 6 and neighboring positions of the protospacer.
- Other: other sequencing outcomes than non-edited and ABE-edited in position 6.
Fig3d
- RNP concentration (µM): X-axis
- ABE 8e NG, CPP5-ABE 8e NG, TAT-ABE 8e NG, ANTP-ABE 8e NG: Y-axis, mCherry-positive (mCherry+) eGFP-negative (eGFP-) to mCherry+ eGFP+ conversion, individual biological replicates. Conversion = ratio of mCherry+ eGFP+ to total mCherry+ events.
Fig 3e and Fig 3f
- Time (ms): X-axis, time relative to the onset of electroretinography (ERG) stimulus.
- Amplitude (nV): Y-axis, ERG amplitude.
Fig 3g,k
Quantification of ERG responses (b-wave amplitude) from rd12 mice whose response curves are shown in e. ABE RNP concentrations are given in µM. 20 µM corresponds to 4.5 µg ABE RNP per eye, 36 µM to 8.1 µg per eye. NaCl, 390 mM NaCl; Suc, 10% sucrose and 200 mM NaCl, Suc+P = 10% sucrose, 200 mM NaCl, 5-fold molar excess of 6×His-CM18-PTD4.
Fig 3h,l
Quantification of genomic DNA editing, analogous to Fig 3b.
Fig 3i,m
Quantification of edited cDNA transcripts, analogous to Fig 3b.
Fig4.zip
Fig4_FC: raw fluorescence cytometry data.
Fig4f: Microscope images and flow cytometry plots for ABE-treated rd12 reporter cells.
Fig 4k.pdf: CryoEM images of ABE RNP lipid nanoparticles (LNPs).
Fig 4.csv
Fig 4b
- Particle diameter (nm): X-axis
- SM102, CL4H6, DODMA-PS: Y-axis, Signal intensity (%) for each LNP.
Fig 4e
- Time (h): X-axis, time since application of LNP.
- Conversion (%): Ratio of mCherry-positive eGFP-positive to all mCherry-positive reporter cells.
Fig 4g
- ABE concentration (nM): X-axis.
- Conversion (%): Ratio of mCherry-positive eGFP-positive to all mCherry-positive reporter cells.
Fig 4h
B-wave amplitude (µV): Y-axis. ERG, b-wave amplitude.
Labels correspond to ABE RNP LNP.
Fig 4i
- Column BC: Particle diameter (nm): X-axis, for series 0%, 1.50%, 2.50% PEG-lipid.
- Column BG: Particle diameter (nM): X-axis, for series 5%, 10% PEG-lipid.
- Signal intensity (%): Y-axis.
Fig 4j
Analogous to Fig 4g
Fig 4m
- Protein, RNP, LNP: X-axis
- Mass spec/A280: ratio of concentrations of ABE in RNP LNP obtained by absorbance at 280 nm and SIL peptide quantification.
Fig 4o
- A6: precise ABE editing in the position 6 of the protospacer.
- A6 + bystander: ABE editing in the position 6 and the neighboring positions of the protospacer.
- Bystander only: ABE editing in other positions than 6 of the protospacer.
- Indels: insertion-deletion editing outcome.
Fig 4p
- On-target, OT1, ... OT10 - distinct mouse genomic sites that may be recognized by the ABE RNP.
- Untreated: Non-treated rd12 reporter cells.
- ABE RNP LNP 2.5%: rd12 reporter cells treated with ABE RNP LNP with 2.5% of the PEG lipid.
Fig 4q, analogous to Figure 4h. Percentage corresponds to PEG lipid.
Fig5.zip
Fig5c-d: Raw flow cytometry data and fluorescence microscopic photographs.
PE-A: fluorescence intensity of mCherry, FITC-A: fluorescence intensity of eGFP.
Fig 5e
Cryo-EM images of PE RNP LNP
Fig5.csv
Fig 5b
- Particle diameter (nm): X-axis
- SM102 d = 270 nm PdI = 0.068, CL4H6 1.5% PEG-DMG d = 298 nm PdI = 0.024, DODMA 1.5% PEG-DMG d = 176 nm PdI = 0.096, SM102 2.5% PEG-DMG d = 194 nm PdI = 0.040: PE-RNP-LNPs with different compositions. given values indicate diameter (d, in nm) and polydispersity index (PdI). Y-axis, Signal intensity (%).
Fig 5f
Mass spec/A280: ratio of concentrations of PE in RNP LNP obtained by absorbance at 280 nm and SIL peptide quantification.
Fig 5h
- A6: precise PE editing of the target adenine.
- A6 + bystander: PE editing of the target adenine and the neighboring bases.
- Bystander only: ABE editing in other positions without the target adenine.
- Indels: insertion-deletion editing outcome.
Fig 5i
- On-target, OT1, ... OT7 - distinct mouse genomic sites that may be recognized by the PE RNP.
- Untreated: Non-treated rd12 reporter cells.
- PE RNP LNP 2.5%: rd12 reporter cells treated with PE RNP LNP with 2.5% of the PEG lipid.
Fig 5j
B-wave amplitude (µV): Y-axis. ERG, b-wave amplitude.
Labels correspond to particular PE RNP LNP.
Fig6.zip
Fig6f
Uncropped immunohistochemical staining images.
- Blue: DAPI (nuclei); green: RPE65; purple: ZO-1 (retinal pigment epithelium marker of tight junctions).
- 1029OS-1, 1029OS-2: rd12 ABE treated.
- rd12-OD: rd12 untreated.
- WT-OD: wild-type.
Fig6h
- WT: C57BL/6J
- Rd12: rd12 - untreated:
- 1003: rd12- treated
Fig6 uncropped gels
Non-cropped immunoblots with marked areas of interest.
Fig6.csv
Fig6b,c
- On-target: precise editing of the target adenine.
- On-target + bystander: editing of the target adenine and the neighboring bases.
- Bystander only: editing in other positions without the target adenine.
- Indels: insertion-deletion editing outcome.
Fig6e
- X-axis: rd12: non-treated rd12 mice; ABE: ABE RNP LNP-treated rd12 mice; PE: PE RNP LNP-treated rd12 mice; WT: wild-type mice.
- Y-axis: amount of 11-cis-retinal (pmol per eye).
Fig 6g
- ERG a-wave, ERG b-wave: Y-axis, Amplitude (microvolts).
- X-axis: rd12: non-treated rd12 mice; ABE: ABE RNP LNP-treated rd12 mice; PE: PE RNP LNP-treated rd12 mice; WT: wild-type mice.
Fig 6h
- Pupillary constriction (%): Y-axis
- X-axis: rd12: non-treated rd12 mice; ABE: ABE RNP LNP-treated rd12 mice; PE: PE RNP LNP-treated rd12 mice; WT: wild-type mice.
Fig 6i
SC evoked responses, V1 evoked responses.
- Time (s), X-axis.
- Amplitude (microvolt), Y-axis.
- Stimulus from time of 0 s to 0.4 s.
Fig_4_5_uncropped_gels.pdf
Non-cropped immunoblots with marked regions of interest.
EDFig1.zip
EDFig1_FC
Raw flow cytometry data.
- FSC-H: forward scatter, height.
- SSC-H: side scatter, height.
- FSC-A: forward scatter, area.
- SSC-A: side scatter, area.
- FITC-A: green (eGFP) fluorescence intensity.
- Pacific Blue-A: Pacific blue (DAPI) fluorescence intensity.
- PE-A: red (mCherry) fluorescence intensity.
EDFig1a
Raw fluorescence microscopic images.
Flow cytometry plots. FITC-A: green (eGFP) fluorescence intensity. PE-A: red (mCherry) fluorescence intensity.
EDFig1.csv
Extended Data Fig 1b
- Conversion(%): Y-axis. Ratio of mCherry-positive (mCherry+) GFP-positive (GFP+) events to total mCherry+ events.
- NE S2: no enzyme, 2% sucrose; PE S2: 500 nM PE RNP, 2% sucrose; NE P S2: no enzyme, 2,500 nM 6xHis-CM18-PTD4 peptide, 2% sucrose; PE P S2: 500 nM PE RNP, 2,500 nM 6xHis-CM18-PTD4 peptide, 2% sucrose; NE S10: no enzyme, 10% sucrose; PE S10 500 nM PE RNP, 10% sucrose; NE P S10: o enzyme, 2,500 nM 6xHis-CM18-PTD4 peptide, 10% sucrose; PE P S10: 500 nM PE RNP, 2,500 nM 6xHis-CM18-PTD4 peptide, 10% sucrose. Direct RNP delivery.
Extended data Fig 1c
Conversion (%): Y-axis, as in Extended data Fig 1b.
Extended Data Fig 1d
- Conversion (%): Y-axis, as in Extended data Fig 1b.
- RNP (nM): X-axis. Concentration of PE-RNP in nmol/L.
EDFig2.zip
EDFig2_FC: raw fluorescence cytometry data. As in EDFig1_FC.
EDFig2b: Non-adjusted fluorescence microscopy images and flow cytometry plots. As EDFig1a.
Extended data Fig 2 uncropped gels.pdf: Non-cropped immunoblots with marked regions ofinterest.
EDFig2.csv
Extended Data Figure 2a
- Total sequencing reads with the specified edit (%): Y-axis.
- ABE7.10, ABE8e, ABE8e N108Q, ABE9: ABE variants delivered by plasmid transfection.
- A6: precise ABE editing in the position 6 of the protospacer.
- A6 + bystander: ABE editing in the position 6 and the neighboring positions of the protospacer.
- Bystander only: ABE editing in other positions than 6 of the protospacer.
- Indels: insertion-deletion editing outcome.
Extended Data Figure 2c
Conversion (%): Y-axis, as in Extended data Fig 1b.
ABE7.10, ABE8e, ABE8e N108Q, Lipofectamine 3000-mediated delivery.
Extended Data Figure 2e
Total sequencing reads with the specified edit (%): Y-axis. As in Extended data Figure 2a. ABE8e NG delivered as plasmid or RNP.
Extended data Figure 2f,g
Electroretinography a-wave and b-wave amplitudes.
rd12: non-treated rd12 mice; ABE8e: rd12 mice treated with direct injection of 25 micromol/L ABE8e RNP and 25% sucrose; ABE8e + 50% L3000: rd12 mice treated with 23.6 micromol/L ABE8e RNP with 50% Lipofectamine 3000 and 25% sucrose; ABE8e + 10% L3000: rd12 mice treated with 23.6 micromol/L ABE8e RNP with 10% Lipofectamine 3000 and 25% sucrose; WT: Non-treated C57BL/6J mice.
EDFig3.zip
EDFig3_FC_ raw flow cytometry data. As in EDFig1_FC.
EDFig3c
Non-modified fluorescence microscopic images comparing DODMA and DODMA-PS RNP LNP.
EDFig3i
Non-modified fluorescence microscopic images and flow cytometry plots. PE: mCherry fluorescence intensity; FITC: eGFP fluorescence intensity.
EDFig3.csv
Extended data Fig 3 d
- Conversion(%): Y-axis, as in Extended data Fig 1b.
- Time (days): length of storage of ABE RNP LNP in indicated temperature before application on the rd12 reporter cells.
Extended data Fig 3 e
- Signal intensity (%): Y-axis.
- Particle diameter (nm): X-axis. Particle diameter measured by dynamic light scattering.
- 20:1, 30:1, 40:1: lipids to sgRNA weight ratio, 1.5% PEG lipid
- 40:1**,* 50:1*, 60:1*: lipids to sgRNA weight ratio, 2.5% PEG lipid
Extended data Fig 3 f
- Conversion (%): Y-axis, as in Extended data Fig 1b.
- ABE RNP (nM): concentration of ABE RNP applied as LNP on the rd12 reporter cells. LNP type as in Extended data Fig 3 e.
Extended data Fig 3h
Size-exclusion chromatography of ABE RNP and ABE RNP LNP, Sephacryl S-500 HR 16/600.
- Elution volume (ml): X-axis.
- Absorbance 260 nm: Y-axis. Absorbance at 260 nm.
Extended data Fig 3 j
- Conversion (%): Y-axis, as in Extended data Fig 1b.
- ABE8e, ABE8e N108Q; ABE RNP LNP with indicated ABE protein.
- ABE8e NT: ABE8e RNP LNP with non-targeting sgRNA.
Extended data Fig 3k
- B-wave amplitude (microvolt): Y-axis
- rd12: non-treated rd12 mice.
- WT: C57BL/6J mice.
- ABE8e 1.5%, ABE8e 2.5%, ABE8e N108Q 2.5%, ABE8e NT 2.5%: ABE RNP LNP with indicated ABE protein, guide RNA and percentage of PEG lipid.
Extended data Fig 3 uncropped gels.pdf
Non-cropped immunoblots with marked regions of interest.
EDFig4.zip
EDFig4.csv
Extended Data Figure 4a
- SC Average VEP: Visually-evoked potentials in superior colliculus.
- Time (s): time relative to stimulus onset. Stimulus time: 0 - 0.4 s.
- Amplitude (microvolts): recorded response.
- VEP Amplitude: recorded response amplitude.
- WT: C57BL/6J mice.
- ABE: rd12 mice treated with ABE RNP LNP.
- PE: rd12 mice treated with PE RNP LNP.
- RNP: rd12 mice treated with ABE RNP, direct injection.
- RPE65-/-: non-treated rd12 mice.
Extended Data Figure 4b
V1 Average VEP: visually-evoked potentials in the primary visual cortex V1.
Data series and stimulus as in Extended Data Figure 4a.
Supplementary_Figure_1.zip
S1.csv
Supplementary Figure 1a-h
- Fluorescence intensity: Y-axis, FRET fluorescence intensity.
- Temperature (°C): X-axis.
- Samples: Indicated protein or RNP with specified additives.
Supplementary_Figure_2.zip
- TIF: Non-modified fluorescence microscopic images of HEK loxP GFP RFP cells treated with Cre fusion proteins.
- EMF: flow cytometry plots of photographed cells. FITC: GFP fluorecence intensity, PE: RFP fluorescence intensity.
- First letter: type of cel-penetrating peptide. A: ANTP; C: CPP5; N: no peptide; T: TAT.
- Subsequent digits: Cre concentration. 01: 100 nM; 0.25: 250 nM; 05: 500 nM; 0.75: 750 nM; 1: 1 miromol/L.
- R[number]: number indicates a replicate.
- 3x3 or 5x5: stitching 3x3 or 5x5, respectively.
- Red: RFP, Green: GFP.
S2.csv
Supplementary Figure 2b
- GFP to RFP conversion (%): Y-axis. Ratio of RFP-positive events to RFP-positive and GFP-positive events.
- Cell viability (%): percentage of DAPI-negative events gated for cells (P1) and single cells (P2).
Supplementary_Figure_3.zip
As in Supplementary_Figure_2. Cre concentration 500 nmol/L. Peptide concentration (micromol/L): concentration of 6xHis-CM18-PTD4 peptide.
Supplementary_Figure_4.zip
As in supplementary_Figure_3. No Cre controls.
Supplementary_Figure_6.zip
S6.csv
Supplementary Figure 6a
Peak area: LC/MS signal for a specified peptide of Cas9, TadA and MMLV RT.
Supplementary Fig 6c
Peptide concentration (mol/L): specific peptide concentration determined for exemplary ABE and PE RNP LNP.
Supplementary Fig 6d
- n (fmol): X-axis. Amount of peptide standard subjected to LC-MS experiment.
- Peak area: Y-axis. Signal corresponding to the specified peptide.
Supplementary Fig 6e
- Relative abundance (%): Y-axis. Normalized signal from LC-MS.
- m/z: X-axis. Mass-to-charge ratio.
Supplementary_Figure_7.zip
S7.csv
Reads with edit(%): Y-axis. Percentage of editing of target adenine (On-tatget) or any nearby bases in the off-target sites (OT1-OT10). Untreated: non-treated rd12 mice. ABE/PE RNP LNP 2.5%: rd12 mice treated with specified RNP LNP with 2.5% PEG lipid.
Supplementary_Figure_8.zip
S8.csv
Supplementary Fig 8a, 8b
Percentage of editing of target adenine in rd12 mice treated with non-targeting ABE- and PE RNP LNP.
Supplementary Fig 8c, 8d
ERG a-wave and b-wave amplitudes recorded for rd12 mice treated with non-targeting ABE- and PE RNP LNP.
Sequencing.zip
Fastq files from amplicon sequencing of cells and mice treated with reagents listed in SraRunTable.csv.
SraRunTable.csv variables:
- Run: Sequencing run identifier.
- Age: Age of the organism.
- Assay type: Sequencing run type.
- AvgSpotLen: Average length of the sequencing read.
- Bases: Total bases in sequencing run.
- BioProject: Project identifier.
- BioSample: Sample identifier.
- BioSampleModel: Sample classification.
- Bytes: File size.
- Center Name: Location of the experiment.
- Collection date: Date of the experiment.
- Consent: Privacy qualifier of the data.
- DATASTORE filetype: File type of the stored data.
- DATASTORE provider: Data storage provider.
- DATASTORE region: Data storage server.
- Experiment: Experiment identifier.
- geo_loc_name_country: Country of the experiment location.
- geo_loc_name_country_continent: Continent of the experiment location.
- geo_loc_name: Location of the experiment.
- Instrument: Name of the instrument.
- Library Name: Name of the experiment.
- LibraryLayout: Layout of the sequencing library.
- LibrarySelection: Technique used to select the sequenced polynucleotide.
- LibrarySource: Type of the template.
- Organism: Organism from which the DNA was isolated.
- Platform: Experimental platform.
- ReleaseDate: The date the data were published.
- create_date: The date the data were deposited.
- Version: Version of the data.
- Sample Name: Name of the file.
- sex: Sex of the organism/cell line.
- SRA Study: Study identifier.
- strain: strain of the organism.
- Tissue: The kind of tissue from which the genetic material was isolated.
- treatment: The type of treatment.
