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Peptide vehicles are not one standard CRISPR delivery product: they are engineered systems that help Cas9-related cargo enter cells, and some also help it escape endosomes. Published approaches have carried Cas9 protein with guide RNA, Cas9 ribonucleoprotein (RNP), CRISPR-Cas9 RNA, or a Cas9 expression plasmid with guide RNA. Their reported results vary by formulation, cargo, cell type and assay, so the percentages from separate studies are not a head-to-head ranking.
What a peptide vehicle does
A peptide vehicle is an engineered peptide or peptide-based formulation used to associate with CRISPR cargo and promote its delivery into cells. The cargo may be a Cas9 protein-guide complex, an RNP, RNA that encodes CRISPR components, or DNA plasmid instructions for producing Cas9 alongside a guide RNA. These formats are not interchangeable: some deliver the editing machinery itself, while others deliver instructions for making it.
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Getting cargo across the cell membrane is only one hurdle. Cargo taken into a cell may remain enclosed in an endosome rather than reach the place where it can function. The PAGE approach, published in 2023, paired cell-penetrating Cas9 or Cas12a with a separate cell-penetrating endosomal-escape peptide, addressing entry and escape as distinct steps.
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How the published approaches differ
| Approach and year | Cargo and delivery strategy | Reported result | How to interpret it |
|---|---|---|---|
| PAGE, 2023 | Cas9 or Cas12a protein, including RNP formats, paired with cell-penetrating and endosomal-escape peptides | The study reports a 30-minute incubation and editing efficiencies upwards of 98% in tested human and mouse primary cells and other tested cell types, including T cells and hematopoietic progenitor cells. | “Upwards of 98%” describes results in the paper’s tested cells and conditions, not an expected rate for other cells or protocols. |
| ADGN, 2024 | Self-assembled peptide nanoparticles carrying CRISPR-Cas9 RNA | The study abstract reports 60% luciferase-gene knockout in vitro and systemic delivery with gene knockout in a mouse orthotopic lung-tumor model. | The in-vitro figure and mouse-model result describe different experimental settings; neither establishes treatment efficacy in people. |
| P-HNP, 2018 | PEGylated nanoparticles with a cationic α-helical polypeptide, carrying a Cas9 expression plasmid and single-guide RNA (sgRNA) | The authors report up to 47.3% in-vitro editing and experiments in a mouse tumor model. | This plasmid-based system has a different cargo from protein/RNP and RNA approaches, so its percentage cannot be ranked directly against theirs. |
| CPP-mediated delivery, 2014 | Cell-penetrating-peptide-conjugated Cas9 protein and cell-penetrating-peptide-complexed guide RNA | The authors report gene disruption in human cell lines and fewer off-target mutations than plasmid transfection in their experiments. | This was a proof of concept using specific conjugation, cell lines and experimental conditions; the finding does not establish a general off-target advantage for peptide delivery. |
| hPep nanoparticles, 2025 | Cell-penetrating peptide nanoparticles carrying RNPs and other gene editors | The PubMed abstract reports base-editing efficiencies of 96% in HEK293T cells, 74% in induced pluripotent stem cells (iPSCs), and 80% in muscle stem cells. | These are base-editing results, not Cas9 nuclease knockout rates, and should not be compared as though they measured the same outcome. |
Why the reported percentages are not a league table
The figures above come from separate studies with different payloads, cell models, doses, assays and experimental settings. A percentage reported for one editor and cell type does not predict the result for another formulation or target. Even when two studies report editing, the numbers are meaningful side by side only if the relevant conditions and measurements match; these reported results do not provide that head-to-head comparison.
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Likewise, a result in cultured cells does not establish delivery or efficacy in an animal, and a mouse-model result does not establish a clinical treatment. The cited studies describe preclinical research; they do not demonstrate therapeutic benefit in people.
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What to look for when evaluating a peptide delivery study
- Identify the cargo. Distinguish delivered Cas9 protein or RNP from Cas9 RNA and from a Cas9 expression plasmid plus guide RNA.
- Check whether the system addresses endosomal escape. Cell entry alone does not show that functional cargo reaches its destination inside the cell.
- Read the model and assay alongside the number. Note the cell type or animal model, the measured editing outcome and the experimental conditions before interpreting an efficiency figure.
- Separate nuclease editing from other editor types. Base-editing percentages, such as those reported for hPep nanoparticles, are not equivalent to Cas9 nuclease knockout results.
- Do not assume a study formulation is a standard product. The reported systems are engineered research formulations; the cited work does not establish a universal carrier, a general-purpose retail kit or a clinical delivery product.
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