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Peptide vehicles are not one standard CRISPR delivery product. They are a family of experimental systems that use engineered peptides to help Cas9 protein, a Cas9–guide RNA complex, CRISPR RNA, or a Cas9-encoding plasmid enter cells. Some designs also address a separate obstacle: getting cargo out of endosomes after uptake. Results depend on the peptide, cargo, cell type and assay, so percentages reported by different studies are not a head-to-head comparison or a promise of what another experiment will achieve.
What a peptide vehicle does
CRISPR components must reach a cell in a form that can function. A peptide-based vehicle can be designed to associate with the editing cargo and promote cellular entry. But uptake is not the same as successful delivery to the place where editing can occur: cargo taken into a cell may remain trapped in an endosome. Some systems therefore pair a cell-penetrating component with a peptide intended to promote endosomal escape.
The distinction matters when interpreting a result. A delivery strategy has to be evaluated in terms of its particular cargo and experimental system, not simply whether it gets material into cells.
How the published approaches differ
| Study and platform | Cargo and approach | Reported result | What the result does and does not show |
|---|---|---|---|
| PAGE, 2023 | Cell-penetrating Cas9 or Cas12a protein, used as protein or ribonucleoprotein (RNP), paired with a cell-penetrating endosomal-escape peptide. | The authors report a 30-minute incubation and editing efficiencies upwards of 98% in tested human and mouse primary cells and cell types, including T cells and hematopoietic progenitor cells. | The figure describes tested cells and conditions in this study, not an expected rate for other cells or protocols. |
| ADGN, 2024 | Self-assembled peptide nanoparticles carrying CRISPR-Cas9 RNA. | The abstract reports 60% luciferase-gene knockout in vitro and systemic delivery with gene knockout in a mouse orthotopic lung-tumor model. | The in-vitro and mouse-model results do not establish treatment efficacy in people. |
| P-HNP, 2018 | PEGylated nanoparticles using a cationic α-helical polypeptide to deliver a Cas9 expression plasmid and single-guide RNA (sgRNA). | The authors report up to 47.3% editing in vitro and experiments in a mouse tumor model. | This plasmid-based approach uses different cargo from protein/RNP or RNA delivery, so its percentage cannot be ranked directly against theirs. |
| CPP-mediated delivery, 2014 | Cell-penetrating peptide (CPP)-conjugated Cas9 protein and CPP-complexed guide RNA. | The authors report gene disruption in human cell lines and fewer off-target mutations than plasmid transfection in their experiments. | This is an early proof of concept; the finding applies to the specific conjugation, cells and experimental design tested. |
| hPep nanoparticles, 2025 | Cell-penetrating peptide nanoparticles for 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 if they measured the same outcome. |
Why the percentages are not a leaderboard
The reported values come from different years, cargo formats, cell types and assays. They may measure different editing outcomes, and some findings are from cell culture while others include animal models. A meaningful comparison would require aligned conditions—including cargo, dose, cell type, delivery route and measurement method. The studies summarized here do not provide a single head-to-head test across all these platforms.
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For example, the 2025 hPep figures refer to base editing, whereas the other named percentages concern outcomes such as gene knockout or editing with different cargo. A larger percentage in one of these reports does not by itself show that its vehicle is generally better.
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The cited work is preclinical: it includes in-vitro experiments and animal-model research. These findings do not establish human clinical efficacy or a therapeutic benefit. Nor do they identify one standardized peptide vehicle that is interchangeable across editing cargos, cell types and applications.
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The systems are study-specific formulations. The findings therefore support the idea that engineered peptides can help deliver CRISPR components in particular experimental settings—not that a general-purpose retail kit or a clinically validated delivery product is available.
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