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OwnerTrevor Percival Castor, Vasudevacharya Jayarama +1inventors
InventorsTrevor Percival Castor, Vasudevacharya Jayarama, James A McSwiggen
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The present invention pertains to the nanoencapsulation of siRNA and other biologics in phospholipid nanosomes for the improved delivery of siRNA and other biologics to targeted diseased human or animal organs and human or animal cells and apparatus and methods for making the same. In embodiments of the present invention, novel siRNAs were designed to down regulate CCR5 and CD4, based on an analysis of all known alternative transcripts for each gene from both human and monkey (Macaca mulatta) genomes. Embodiments of the present invention feature supercritical, critical and near critical fluids. Embodiments of the present invention also pertain to down regulation of CXCR4 receptor and targeting of nanosomes containing specific siRNA sequences to cells expressing those receptors on the cell surface by coating them with specific ligands. These include ligands for the receptors CCR5, CD4 and CXCR4.
A CCR5 (Cysteine-Cysteine Chemokine Receptor 5) siRNA (small interfering Ribonucleic Acid) gene sequence for human and monkey (Macca mulatta) genomes, comprising a 19-mer fragment matching 5′UTR (5′ Untranslated Region), 3′UTR (3′ Untranslated Region) or CDS (CoDing Sequence), the fragment having a GC (guanine-cytosine) content between 30% and 50%, wherein the seed sequence of the siRNA at positions 2-7 or 2-8 of the antisense strand is also present in miRNA (micro RNA), and wherein the siRNA has a 100% sequence homology between all human and monkey alternative transcripts and fewer than 120 13-mer hits.
A CD4 (Cluster of Differentiation 4) siRNA gene sequence for human and monkey (Macca mulatta) genomes, comprising a 19-mer fragment matching 5′UTR, 3′UTR or CDS, the fragment having a GC content between 30% and 50%, wherein the seed sequence of the siRNA at positions 2-7 or 2-8 of the antisense strand is also present in miRNA, and wherein the siRNA has a 100% sequence homology between all human and monkey alternative transcripts and fewer than 160 13-mer hits.
A CXCR4 (C-X-C Chemokine Receptor type 4) siRNA gene sequence for human and monkey (Macca mulatta) genomes, comprising a 19-mer fragment matching 5′UTR, 3′UTR or CDS, the fragment having a GC content between 30% and 50%, wherein the seed sequence of the siRNA at positions 2-7 or 2-8 of the antisense strand is also present in miRNA, and wherein the siRNA has a 100% sequence homology between all human and monkey alternative transcripts and fewer than 160 13-mer hits.
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