MicroRNA Therapeutics for Treating Genetic Diseases:
A number of RNAi-based therapeutics are currently in late stage preclinical development. The recent identification of endogenous 'housekeeper' microRNAs that may dysfunction in disease suggests a myriad of applications for RNAi for treating genetically complex diseases. The molecular basis of RNA interference is well established, but the successful use of RNAi in therapeutic situations requires the delivery of RNA across the cell membrane. There are a variety of current methods for RNAi delivery such as: transfection, elctroporation, injection, liposome-facilitated transport, and microinjection. All of these methods are unsatisfactory for therapeutic use due to low-efficiency delivery and/or a lack of practical utility of delivery. A high-efficiency method that could work for delivering RNA to cells in vivo would drastically improve the therapeutic potential of RNAi.
RNAi Delivery to Cells for Therapeutic Benefits:
This invention consists of a double-stranded RNA (dsRNA) molecule (with sequence for RNA interference), a cell-penetrating peptide, and a covalent band between the two. When the cell-penetrating peptide is contacted with a cell the dsRNA is delivered to the cell. This invention also includes a method of using the technology described to identify the phenotypes resulting from dsRNA delivery to the cell. The cell penetrating peptide consists of a short (12-30 amino acid) sequence that confers non-endocytic translocation properties on an associated complex. One example of such a peptide is penetratin.
Applications:
• Delivery of RNAi to cells to decrease expression of a gene
• Delivery of RNAi for therapeutic purposes
• Screens to identify sequences which inhibit gene function
Advantages:
• Efficiency of delivery is high (100% in tested neuronal cells)
• Method of delivery is simple
• Ease of use makes large scale screening possible
