Aptamers for personal health care applications
Inventors
Velasquez, Juan Esteban • Rupard, Spencer Christopher • Trejo, Amy Violet • PITZ, Adam Michael • Schmeichel, Kelly Lee • Swigart, Erin Nicole • Penner, Gregory Allen • NAMANJA-MAGLIANO, Hilda Andamiche • Wagner, Matthew Scott
Assignees
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Abstract
An aptamer composition is disclosed which has one or more oligonucleotides that include at least one of deoxyribonucleotides, ribonucleotides, derivatives of deoxyribonucleotides, derivatives of ribonucleotides, or mixtures thereof. The aptamer composition has a binding affinity for one or more cellular membrane glycoproteins selected from the group consisting of: intercellular adhesion molecule 1 (ICAM-1), low-density lipoprotein receptor (LDLR) family members, and cadherin-related family member 3 (CDHR3), preferably intercellular adhesion molecule 1 (ICAM-1), and is configured to reduce the binding of one or more human rhinoviruses to the intercellular adhesion molecule 1 (ICAM-1).
Core Innovation
The invention concerns an aptamer composition that has a binding affinity for intercellular adhesion molecule 1 (ICAM-1) and is configured to reduce the binding of one or more human rhinoviruses to ICAM-1. The aptamer composition includes at least one oligonucleotide comprising from about 30 to about 60 nucleotides truncated from parent oligonucleotides, and the truncated aptamers comprise a GAGGYYZ motif, wherein Y is absent or A and Z is absent or G, C, A, T or U.
The disclosure extends to personal health care composition formats and to inhibiting human rhinovirus infection by inhibiting binding of the human rhinovirus to ICAM-1 on epithelial cells. The personal health care composition comprises the same ICAM-1-binding aptamer composition, and the method applies the aptamer composition to inhibit human rhinovirus infection by reducing binding of the virus to ICAM-1.
The aptamers are also described as having nanomolar affinity or low kD for ICAM-1 by SPR and lacking significant binding to human serum albumin, supporting specificity toward ICAM-1. Specificity rationale is described using counter-selection and ICAM receptor domain or epitope alignment, and motif and secondary-structure requirements are supported by enrichment of the GAGGYYZ motif in effective aptamers and temperature-dependent binding analysis using mutated NasD-4.1 variants.
Claims Coverage
The document includes three independent claims, covering an aptamer composition, a personal health care composition, and a method of inhibiting human rhinovirus infection. Across the independent claims, the central inventive requirements include ICAM-1 binding with reduced rhinovirus binding, truncated oligonucleotides in the 30–60 nucleotide range, sequence identity constraints to SEQ ID NO: 1–200, and a GAGGYYZ motif with defined Y and Z allowances.
Truncated ICAM-1-binding aptamer composition configured to reduce rhinovirus binding
An aptamer composition comprising at least one oligonucleotide consisting of deoxyribonucleotides, ribonucleotides, derivatives of deoxyribonucleotides, derivatives of ribonucleotides, or mixtures thereof, wherein the aptamer composition has a binding affinity for ICAM-1 and is configured to reduce the binding of one or more human rhinoviruses to ICAM-1, and wherein the aptamer composition comprises at least one oligonucleotide comprising from about 30 to about 60 nucleotides truncated from parent oligonucleotides and a GAGGYYZ motif with specified Y and Z constraints.
Personal health care composition containing truncated ICAM-1-binding aptamer composition
A personal health care composition comprising the same ICAM-1-binding aptamer composition with truncated oligonucleotides and a GAGGYYZ motif, configured to reduce the binding of one or more human rhinoviruses to ICAM-1.
Method of inhibiting human rhinovirus infection by applying ICAM-1-binding truncated aptamer composition to epithelial cells
A method of inhibiting human rhinovirus infection by inhibiting binding of the human rhinovirus to intercellular adhesion molecule 1 (ICAM-1) of epithelial cells by applying the same aptamer composition.
Across the independent claims, the claim coverage centers on ICAM-1-binding aptamer compositions containing truncated oligonucleotides of about 30 to about 60 nucleotides that are configured to reduce binding of one or more human rhinoviruses to ICAM-1, with truncated aptamers including the GAGGYYZ motif under specified constraints.
Stated Advantages
Configured to reduce binding of one or more human rhinoviruses to ICAM-1.
Inhibits human rhinovirus infection by inhibiting binding of the human rhinovirus to ICAM-1 of epithelial cells.
Strong viral inhibition of Rhinovirus Type 14 reported as log10 viral titer reductions and % inhibition.
Selective binding of ICAM-1-binding aptamers to nasal epithelial cells (HNEpC) but not ICAM-1-negative HEK293.
Nanomolar affinity or low kD for ICAM-1 by SPR.
Lack of significant binding to human serum albumin.
Documented Applications
Personal health care composition for upper respiratory delivery, including nasal and oral dosage forms.
Inhibiting human rhinovirus infection by applying an ICAM-1-binding aptamer composition to epithelial cells, including delivery to the upper respiratory tract by spraying.
Reducing binding of one or more human rhinoviruses to ICAM-1 on epithelial cells, as a method of inhibiting human rhinovirus infection.
Use in a personal health care composition.
Inhibition of Rhinovirus Type 14 infection or binding on H1-HeLa cells in the experimental evidence described in the partial content.
Targeting nasal epithelial cells (HNEpC) as described in the experimental evidence.
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