The Coiled‐Coil Forming Peptide (KVSALKE)5 Is a Cell Penetrating Peptide that Enhances the Intracellular Delivery of Proteins
Open accessAbstract
Protein‐based therapeutics have the potential to treat a variety of diseases, however, safe and effective methods for delivering them into cells need to be developed before their clinical potential can be realized. Peptide fusions have great potential for improving intracellular delivery of proteins. However, very few peptides have been identified that can increase the intracellular delivery of proteins, and new peptides that can enhance intracellular protein delivery are greatly needed. In this report, the authors demonstrate that the coiled‐coil forming peptide (KVSALKE)5 (termed K5) can function as a cell penetrating peptide (CPP), and can also complex other proteins that contain its partner peptide E5. It is shown here that GFP and Cas9 fused to the K5 peptide has dramatically enhanced cell uptake in a variety of cell lines, and is able to edit neurons and astrocytes in the striatum and hippocampus of mice after a direct intracranial injection. Collectively, these studies demonstrate that the coiled‐coil forming peptide (KVSALKE)5 is a new class of multifunctional CPPs that has great potential for improving the delivery of proteins into cells and in vivo.
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The sgRNA used targets the STOP sequence upstream of the tdTomato gene and enables tdTomato gene expression.
“The sgRNA used in these experiments targets the STOP sequence upstream of the fluorescent tdTomato gene and enables tdTomato gene expression, resulting in fluorescence (Figure 1C) as we previously reported (43).”
From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [43]
MC3 LNP Cas9 mRNA/Ai9 sgRNA demonstrates similar or better local transfection efficiency in the striatum and the hippocampus compared to previously demonstrated results using Cas9 RNPs (37, 43).
“MC3 LNP Cas9 mRNA/Ai9 sgRNA demonstrates similar or better local transfection efficiency in the striatum and the hippocampus compared to previously demonstrated results using Cas9 RNPs (37, 43).”
From Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection (2023) · cites this paper as [43]
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- Authors
- Li, J., Tuma, J., Han, H., Kim, H., Wilson, R. C., Lee, H. Y., & Murthy, N.
- Affiliations
- Innovative Genomics Institute (US)
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Lee, Hye Young
- Murthy, Niren
- Venue
- Advanced Healthcare Materials
- Publisher
- Wiley
- Published
- 2021-12-16
- Volume
- 11
- Issue
- 9
- Pages
- e2102118-e2102118
- ISSN
- 2192-2640 (ISSN-L)
- 2192-2659
- PMC
- PMC9766156
- OpenAlex
- W3217571889
- Cited by
- 16
- References
- 46
- Citations by year
- 2026: 4 · 2024: 4 · 2023: 5 · 2022: 3
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Advanced Healthcare Materials (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institute of Mental Health (R01MH125979)
- National Institute on Drug Abuse (R61DA048444)
- National Human Genome Research Institute (U24HG010423)
- National Institute of Allergy and Infectious Diseases (1UM1AI164559)
- National Institute of Neurological Disorders and Stroke (UG3NS115599)
- National Institute on Aging (R21AG072423)
- Simons Foundation Autism Research Initiative (#574967)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Keywords
- cell-penetrating peptides, intracellular protein delivery, peptide fusion, green fluorescent protein, Cas9, CRISPR/Cas9 genome editing, intracranial injection, striatum, hippocampus, neurons, astrocytes, in vivo delivery
- MeSH terms
- Animals, Biological Transport, Proteins, Mice, Cell-Penetrating Peptides
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