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Patent Pick: Delivering on mRNA's Promise

October 13, 2017 | Contact Author | By: Rachel Grabenhofer
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WomanDNAGenes850

Keywords: CRISPR | mRNA | amino ester | patent | nanomaterial | Ohio State Innovation Foundation | biodegradable | Cas9 protein

Abstract: News about CRISPR and the Cas9 enzyme has permeated nearly every scientific—and even some consumer—communities. But there is one crucial area where these entities have not penetrated to any real appreciable level: the human body. A new patent may fix that.

As many cosmetic scientists are aware, CRISPR and its related Cas9 enzyme are becoming more widely used for gene editing in biological and therapeutic applications. However, according to inventors at the Ohio State Innovation Foundation, possible off-target effects can cause significant safety issues. As such, one alternative is to express Cas9 using its related messenger RNA (mRNA). 

Indeed, mRNA-based therapeutics have shown great promise for expressing functional antibodies and proteins. But therein lies the challenge: Cas9 mRNA, in particular, has a large size (up to 4.5 k nucleotides), a high density of negative charges and weak tolerance of enzymes. Thus, new biomaterials are needed to overcome these obstacles to improve its delivery, both systemically and topically.

Recently, efforts have been made to systemically deliver mRNA using liposomes, polymeric nanoparticles and mRNA-protein complexes, but new carriers are still needed to improve delivery efficiency and maximize mRNA therapies. Some lipid and lipid-like nanoparticles (LNPs and LLNs) have been shown to efficiently deliver RNAs including siRNA, miRNA and mRNA. However, these compounds are not considered biodegradable.

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As many cosmetic scientists are aware, CRISPR and its related Cas9 enzyme are becoming more widely used for gene editing in biological and therapeutic applications. However, according to inventors at the Ohio State Innovation Foundation, possible off-target effects can cause significant safety issues. As such, one alternative is to express Cas9 using its related messenger RNA (mRNA). 

Indeed, mRNA-based therapeutics have shown great promise for expressing functional antibodies and proteins. But therein lies the challenge: Cas9 mRNA, in particular, has a large size (up to 4.5 k nucleotides), a high density of negative charges and weak tolerance of enzymes. Thus, new biomaterials are needed to overcome these obstacles to improve its delivery, both systemically and topically.

Recently, efforts have been made to systemically deliver mRNA using liposomes, polymeric nanoparticles and mRNA-protein complexes, but new carriers are still needed to improve delivery efficiency and maximize mRNA therapies. Some lipid and lipid-like nanoparticles (LNPs and LLNs) have been shown to efficiently deliver RNAs including siRNA, miRNA and mRNA. However, these compounds are not considered biodegradable.

Therefore, according to the present inventors, materials with biodegradable bonds are needed to enable rapid elimination from plasma and tissues, as well as improve tolerability in preclinical studies.The compounds, composition and methods disclosed in this patent application are said to address these needs.

Biodegradable amino-ester nanomaterials for nucleic acid delivery 
WIPO Patent Application WO/2017/176974
Publication date: Oct. 12, 2017
Assignee: Ohio State Innovation Foundation

Described in this patent application is a series of biodegradable, amino-ester lipid-like nanoparticles for the delivery of therapeutic, diagnostic or prophylactic agents (for example, polynucleotides). While topical cosmetics are not outrightly specified, this invention could hold clues to speed the integration of epigenetics into novel products.

In certain embodiments, the nanoparticles are used for the delivery of nucleic acids, small molecules, organometallic compounds, proteins, peptides, polynucleotides, metals, targeting agents, isotopically labeled chemical compounds, drugs, vaccines, immunological agents or agents useful in bioprocessing. In others, the agent is a polynucleotide such as DNA or RNA; specifically RNAi, dsRNA, siRNA, shRNA, miRNA or antisense RNA.