Polyplex-saponin Covalent Conjugate

Simple SummaryContent extracted from patent full text and abstract with AI.

This invention describes a new, non-viral system for delivering nucleic acids, such as DNA or RNA, into cells. The core concept is a polyplex (a complex between a nucleic acid and a cationic polymer) that incorporates a special type of saponin, a molecule known for helping compounds escape from endosomes within the cell. The saponin is attached to the polymer by a linker that only releases the saponin under the acidic conditions found inside endosomes. This release of saponin enhances the ability of the nucleic acid to escape into the cytosol, improving gene delivery effectiveness without harming the cells. Additionally, the system can be modified to specifically target certain cell or tissue types by adding appropriate ligands, potentially enabling highly targeted gene therapies.

Use CasesContent extracted from patent full text and abstract with AI.

• Gene therapy for genetic diseases by efficiently delivering therapeutic genes into patient cells without using viral vectors.
• Cancer therapy, where therapeutic nucleic acids or toxin genes are delivered specifically to cancer cells using targeted ligands.
• Delivery of CRISPR/Cas gene editing components to specific tissues for genome editing applications.
• Development of personalized gene therapies requiring efficient and safe intracellular delivery of large nucleic acids.
• Systemic delivery of nucleic acid drugs in conditions that require minimal off-target effects and maximized efficacy, such as hemophilia B or solid tumors.

BenefitsContent extracted from patent full text and abstract with AI.

• Enables efficient delivery and endosomal escape of gene therapeutics, overcoming a major bottleneck in non-viral gene delivery systems.
• Reduces or eliminates reliance on viral vectors, increasing safety and reducing immunogenicity and manufacturing complexity.
• Low toxicity and minimal negative impact on cell viability, which is superior to existing transfection agents at similar efficacy.
• Flexibility in targeting—can be directed to specific cell or tissue types, minimizing off-target effects and increasing clinical potential.
• Compatible with a wide range of nucleic acids, including large DNA constructs, mRNA, and gene editing tools such as CRISPR/Cas.
• Scalable and potentially lower cost, simplifying the path to manufacturing and commercialization of gene therapies.

Technical Classifications (CPCs)

Inventors & Applicants

Patent Abstract

The invention lies in the field of delivery of nucleic acids into a cell. In particular, disclosed herein is a nucleic acid that is polyplexed with a polymeric scaffold, which scaffold is covalently bound to an endosomal escape-enhancing saponin by a linker configured to release the saponin from the scaffold under conditions present in an endosome. Surprisingly, the presence of the saponin and the linker does not interfere with or affect the ability of the polymeric scaffold to form or maintain the polyplex in the presence of the nucleic acid. Furthermore, such saponin-containing polyplexes not only enhance the cytosolic delivery of the nucleic acid into cells but also do not negatively impact the viability of these cells. The disclosed herein compositions and methods may further be cell-targeted by conjugation to cell- and/or tissue-specific ligands, and, advantageously, exploited in the treatment of various diseases and/or conditions by systemic delivery.