The DOI matches its Crossref record; 55 of the 59 references it cites were found in a registry or an index.
shRNA and siRNA delivery to the brain
Open accessAbstract
The limiting factor in in vivo RNA interference (RNAi) is delivery. Drug delivery methods that are effective in cell culture may not be practical in vivo for intravenous RNAi applications. Nucleic acid drugs are highly charged and do not cross cell membranes by free diffusion. Therefore, the in vivo delivery of RNAi therapeutics must use targeting technology that enables the RNAi therapeutic to traverse biological membrane barriers in vivo. For RNAi of the brain, the nucleic acid-based drug must first cross the brain capillary endothelial wall, which forms the blood-brain barrier (BBB) in vivo, and then traverses the brain cell plasma membrane. Similar to the delivery of non-viral gene therapies, plasmid DNA encoding for short hairpin RNA (shRNA) may be delivered to the brain following intravenous administration with pegylated immunoliposomes (PILs). The plasmid DNA is encapsulated in a 100 nm liposome, which is pegylated, and conjugated with receptor specific targeting monoclonal antibodies (MAb). Weekly, intravenous RNAi with PILs enables a 90% knockdown of the human epidermal growth factor receptor, which results in a 90% increase in survival time in mice with intra-cranial brain cancer. Similar to the delivery of antisense agents, short interfering RNAi (siRNA) duplexes can be delivered with the combined use of targeting MAb's and avidin-biotin technology. The siRNA is mono-biotinylated in parallel with the production of a conjugate of the targeting MAb and streptavidin. Intravenous RNAi requires the combined use of RNAi technology and a drug targeting technology that is effective in vivo.
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“While RNAi holds great promise for treating genetic associated neurological disorders, efficient delivery of siRNA into the brain is still a remarkable obstacle to the clinical applications.[99–101]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [99]
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Cites
The blood-brain barrier: Bottleneck in brain drug development
Pardridge, W. M. (2005) · NeuroRX · doi:10.1602/neurorx.2.1.3 · Cited by 2,798
Nicholson, R., Gee, J., & Harper, M. (2001) · European Journal of Cancer · doi:10.1016/s0959-8049(01)00231-3 · Cited by 2,132
Green, N. M. (1975) · Advances in protein chemistry · doi:10.1016/s0065-3233(08)60411-8 · Cited by 1,472
Gene silencing in mammals by small interfering RNAs
McManus, M. T., & Sharp, P. A. (2002) · Nature Reviews Genetics · doi:10.1038/nrg908 · Cited by 1,400
Antisense Oligonucleotides as Therapeutic Agents—Is the Bullet Really Magical?
Stein, C., & Cheng, Y. C. (1993) · Science · doi:10.1126/science.8351515 · Cited by 1,300
Chiu, Y., & Rana, T. M. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00652-4 · Cited by 400
Pardridge, W. M., Buciak, J. L., & Friden, P. M. (1991) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)20567-5 · Cited by 358
Zhang, Y., Zhang, Y., Bryant, J., Charles, A. C., Boado, R. J., & Pardridge, W. M. (2004) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-03-0740 · Cited by 330
EGF mutant receptor vIII as a molecular target in cancer therapy.
Kuan, C., Wikstrand, C. J., & Bigner, D. D. (2001) · Endocrine Related Cancer · doi:10.1677/erc.0.0080083 · Cited by 325
Pardridge, W. M., Kang, Y., Buciak, J. L., & Yang, J. (1995) · Pharmaceutical Research · doi:10.1023/a:1016244500596 · Cited by 324
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Metadata
- Authors
- Pardridge, W. M.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Pardridge, William M.
- Venue
- Advanced Drug Delivery Reviews
- Publisher
- Elsevier BV
- Published
- 2007-03
- Volume
- 59
- Issue
- 2-3
- Pages
- 141-152
- ISSN
- 0169-409X (ISSN-L)
- PMC
- PMC3572210
- OpenAlex
- W2031687291
- Cited by
- 176
- References
- 59
- Citations by year
- 2025: 4 · 2024: 6 · 2023: 9 · 2022: 6 · 2021: 8 · 2020: 6 · 2019: 10 · 2018: 4 · 2017: 10 · 2016: 6 · 2015: 8 · 2014: 3 · 2013: 18 · 2012: 12
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Advanced Drug Delivery Reviews (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (R01NS053540)
- 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
- RNA interference, shRNA delivery, siRNA delivery, brain, blood-brain barrier, monoclonal antibody targeting, intravenous administration, epidermal growth factor receptor, brain cancer, nucleic acid drug delivery, membrane crossing
- MeSH terms
- Animals, Brain, Carrier Proteins, Humans, Plasmids, Reproducibility of Results, Drug Delivery Systems, RNA, Small Interfering
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