PPMO project management Peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) represent a cutting-edge class of synthetic molecules demonstrating significant promise in various therapeutic applications. These innovative compounds combine the targeted gene-silencing capabilities of phosphorodiamidate morpholino oligomers (PMOs) with the enhanced delivery and specificity offered by peptides. This synergistic approach allows for precise interaction with cellular targets, opening new avenues for combating diseases ranging from infectious pathogens to genetic disorders作者:EK Sully·2016·被引用次数:69—Peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO)restores carbapenem susceptibility to NDM-1-positive pathogensin vitro and in vivo · Abstract..
At their core, PPMOs are synthetic compounds that have a structure similar to DNA or RNA. However, unlike natural nucleic acids, the morpholino backbone of PMOs is uncharged, which contributes to their unique properties and stabilityMolecular properties and intramolecular interactions of .... The fundamental mechanism of action for these oligonucleotides involves binding to specific messenger RNA (mRNA) sequencesPeptide-Conjugated Phosphorodiamidate Morpholino .... This binding event is designed to specifically bind to mRNA and prevent the translation of that mRNA into a target protein. By inhibiting protein synthesis, PPMOs can effectively downregulate the expression of disease-causing genes or essential genes in pathogens作者:M Prescott—Inhibition of Interferon Alpha by aPeptide-Conjugated Phosphorodiamidate Morpholino OligomerIncreases Influenza Virus Replication in Chicken ....
The integration of peptides onto the PMO structure, through a process known as conjugation, is a critical advancement. These peptides can be engineered to possess specific properties, such as the ability to target particular cell types or tissues, or to facilitate cellular uptake. For instance, certain cell-penetrating peptides (CPPs), like the arginine-rich CPPs mentioned in research, can significantly enhance the delivery of the PMO into cells. This improved cellular penetration is crucial for the efficacy of antisense therapies, as it ensures that the therapeutic molecule reaches its intracellular target. The uncharged morpholino oligomer conjugated through a linker to a cell-penetrating peptide forms the basis of the PPMO structure, enabling it to overcome cellular barriers more effectively.
One of the most compelling applications of peptide-conjugated phosphorodiamidate morpholino oligomers lies in the fight against antibiotic resistance. Research has shown that PPMOs can restore susceptibility to antibiotics in multidrug-resistant bacteriaSeveral studies have demonstrated the efficacy of CPP-conjugatedPMOs in delivering them into various cell types and tissues, including zebrafish embryos, .... For example, studies have demonstrated that peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) can restore carbapenem susceptibility to NDM-1-positive pathogens both *in vitro* and *in vivo*. This is a significant breakthrough, as it offers a potential strategy to re-sensitize infections that have become resistant to current treatment optionsPeptide-conjugated phosphorodiamidate morpholino ... - PMC. Furthermore, PPMOs targeting essential genes in bacteria have the potential of being used as antisense antibiotics to treat infections caused by challenging pathogens作者:EK Sully·被引用次数:69—Phosphorodiamidate morpholino oligomers (PMOs) are syn- thetic nucleotide analogues that are thought to prevent transla- tion of a specific gene by selectively ....
Beyond infectious diseases, PPMOs are also being explored for their potential in treating genetic disorders. In Duchenne muscular dystrophy (DMD), a severe genetic disease characterized by progressive muscle degeneration, PPMOs have shown promise in restoring dystrophin production. Specifically, phosphorodiamidate morpholino oligomers (PMOs) are an antisense RNA platform that is used clinically in patients with DMD to facilitate exon skipping, a process that can correct the genetic defect and allow for the production of a functional dystrophin protein. The conjugation of these PMOs with specific peptides can further enhance their delivery to muscle tissue, thereby improving their therapeutic efficacy.Phosphorodiamidate morpholino oligomers(PMOs) are an antisense RNA platform that is used clinically in patients with DMD to facilitate exon skipping and ... For instance, research has investigated using muscle homing peptide CyPep10 as a conjugate to phosphorodiamidate morpholino oligomers (PMOs) to improve muscle-specific delivery.2008年4月22日—We discuss the chemistry, sequence specificity, stability and toxicity of Morpholinos when covalentlyconjugatedwith cell-penetratingpeptides...
The synthesis of peptide-conjugated phosphorodiamidate morpholino oligonucleotides involves sophisticated chemical processes to ensure the precise attachment of the peptide to the morpholino backbone, often via a linker molecule2012年9月14日—Antisensephosphorodiamidate morpholino oligomers(PMOs) and their derivatives downregulate target gene expression in a sequence-dependent .... The sequence specificity of the PMO is paramount, ensuring that it binds only to its intended mRNA target, thereby minimizing off-target effects. The resulting peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) is a highly engineered molecule designed for potent and specific biological activity.作者:S Bittner·2023—PPMOs consist of anuncharged morpholino oligomer conjugated through a linker to a cell-penetrating peptide(CPP) and are designed to bind cellular RNAs ...
In summary, peptide-conjugated phosphorodiamidate morpholino oligomers represent a powerful and versatile therapeutic modality. Their ability to precisely target mRNA, coupled with enhanced cellular delivery facilitated by peptide conjugation, positions them as a significant advancement in the development of novel treatments for a wide range of conditions, including antibiotic-resistant infections and genetic diseases like DMD. The ongoing research and development in this field continue to uncover new applications and refine existing strategies, solidifying the role of PPMO technology in the future of medicine.
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