Cationic Polymer with Alkyl Side Chains Hydrolysable Polymer Carriers for Nucleic Acid and Polypeptide Delivery

This patent covers a family of biodegradable cationic polymers designed to package and deliver large therapeutic molecules (nucleic acids such as siRNA and mRNA, gene editing payloads, and polypeptides) into target cells, with a hydrolysable backbone, hydrophobic side chains for cell membrane interaction, and oligoamine or polyamine side chains for binding negatively charged cargo.

The Problem

Peptide, protein, and nucleic-acid drugs have revolutionised what is treatable. Antisense oligonucleotides, siRNA, mRNA vaccines, gene editing tools (CRISPR), and therapeutic proteins all exist as approved or near-approved medicines. The persistent rate-limiting problem is delivery: large, charged biomolecules cannot cross cell membranes on their own, are degraded in extracellular fluid, and are filtered out by the liver and spleen before reaching their target tissue. Lipid nanoparticles (LNPs) have become the dominant delivery vehicle for mRNA, but LNPs are constrained by manufacturability, biodistribution that is heavily liver-biased, and immune effects. Cationic polymers (such as PEI) are a parallel class that complex with nucleic acids electrostatically but suffer from chronic toxicity from non-degradable backbones. The need is for cationic polymer carriers that protect and deliver large molecules with controllable biodistribution, low cytotoxicity, and a backbone that hydrolyses to safe fragments after cargo release.

What This Invention Does

The invention provides a polymer with a hydrolysable backbone bearing two or three distinct types of side chain along its length. Monomer units of type (i) carry a hydrophobic side chain (typically an alkyl group) that drives interactions with cell membranes and helps the polymer assemble into particles in aqueous environment. Monomer units of type (ii) carry an oligoamine or polyamine side chain (a primary, secondary, or tertiary amine string) that provides positive charges to complex negatively charged nucleic acids and to mediate endosomal escape via proton-sponge behaviour. Optional monomer units of type (iii) carry an ionisable group with a pKa typically below 7, allowing the polymer’s net charge to shift on acidification inside the endosome. The polymer of Formula 1 specified in the patent allows independent tuning of each monomer type and ratio across a broad sequence space, and the patent covers both the polymer compositions, methods for preparing them, and methods of delivering a nucleic acid and/or polypeptide to a cell using the polymer. The application is a divisional of AU 2020263474, claiming priority from US provisional applications filed April and May 2019.

Key Features

• Hydrolysable backbone. The polymer is designed to break down over time into smaller fragments. This addresses the chronic-toxicity problem of non-degradable cationic polymers like polyethyleneimine while preserving the delivery advantages of polymeric carriers.
• Three side-chain functional units. Independent monomers carry hydrophobic side chains, polyamine side chains, and (optionally) ionisable side chains, so the membrane interaction, nucleic acid complexation, and endosomal escape behaviour can each be tuned independently.
• Defined Formula 1 chemistry. The patent describes a precise polymer formula with substitutable side chains and integer ranges for the monomer counts, giving a discoverable composition space for screening and patenting of leads.
• Cargo flexibility. The polymer is claimed for delivery of both nucleic acids (DNA, mRNA, siRNA, gRNA for CRISPR) and polypeptides, opening a single carrier platform across multiple drug modalities.
• Manufacturing tractability. As a polymer rather than a lipid nanoparticle, the carrier can be produced through standard polymer chemistry and characterised with standard analytics, potentially simplifying the supply chain compared with LNP processes.

Who Is Behind It?

The applicant is GenEdit Inc., a California-based gene editing delivery company founded out of UC Berkeley to develop non-viral, non-lipid polymer nanoparticles for the delivery of gene editing payloads to specific tissues. The named inventors are Santanu Maity, Franco Duarte, and Kunwoo Lee. Kunwoo Lee is GenEdit’s co-founder and chief executive. The Australian patent attorney is Spruson and Ferguson in Sydney. The application is a divisional of AU 2020263474, with priority from US provisional applications 62/837,658 (23 April 2019) and 62/853,658 (28 May 2019).

Why It Matters

The current generation of cell and gene therapies and mRNA medicines depends almost entirely on viral vectors (AAV, lentivirus) or lipid nanoparticles for delivery. Both have well-known limits: viral vectors raise immunogenicity and capacity constraints, LNPs concentrate in the liver. Polymer-based delivery platforms that can be engineered for non-liver biodistribution open up tissue-specific gene editing and RNA therapeutics for indications outside the current LNP and AAV envelope. GenEdit’s NanoGalaxy polymer platform is one of the leading non-LNP, non-viral delivery systems in development and is the subject of partnership and licensing discussions with major pharmaceutical companies. Australian patent rights over the polymer composition itself, rather than only its application, are commercially central to that licensing position and to any local manufacturing or clinical-trial work that arises from those partnerships.

Related Concepts

Polymeric carriers sit alongside lipid nanoparticles and viral vectors such as AAV in the broader field of nanoparticle drug delivery, where the central challenge is moving large, charged molecules safely into the right cells.

The cargo classes the polymer is designed to ferry, including siRNA, mRNA, and CRISPR guide RNAs, are some of the most active modalities in modern drug development, and biodistribution beyond the liver remains the field’s largest open problem.

---

AU 2026201855 was published in the Australian Official Journal of Patents on 2 April 2026 and is open for public inspection. Patent applications represent inventions that are sought to be protected and do not necessarily reflect commercially available products.