Invention Title:

BRANCHED POLY(-AMINO ESTERS) FOR THE DELIVERY OF NUCLEIC ACIDS

Publication number:

US20260124155

Publication date:

2026-05-07

Section:

Human necessities

Class:

A61K9/5153

Inventors:

Robert S. Langer 🇺🇸 Newton, MA, United States

Carlo Giovanni TRAVERSO 🇺🇸 Newton, MA, United States

Yunhua SHI 🇺🇸 Belmont, MA, United States

Daniel REKER 🇺🇸 Durham, NC, United States

James Byrne 🇺🇸 Boston, MA, United States

HYUNJOON KIM 🇺🇸 CAMBRIDGE, MA, United States

Gary W. Liu 🇺🇸 Cambridge, MA, United States

Grace Junyue Zhong 🇺🇸 Cambridge, MA, United States

Ameya R. Kirtane 🇺🇸 Minneapolis, MN, United States

Netra Rajesh Rajesh 🇨🇦 Brampton, Canada

Assignees:

MASSACHUSETTS INSTITUTE OF TECHNOLOGY 🇺🇸 Cambridge, MA, United States

The Brigham and Women's Hospital Inc. B 🇺🇸 Boston, MA, United States

Applicants:

The Brigham and Women's Hospital Inc. 🇺🇸 Boston, MA, United States

Massachusetts Institute of Technology 🇺🇸 Cambridge, MA, United States

Smart overview of the Invention

Branched Poly(β-amino esters) (PBAEs) are synthesized by reacting primary amines with diacrylates, resulting in polymers of Formula (I). These polymers are designed for the delivery of nucleic acids into cells, addressing challenges associated with the large size and charge of nucleic acids which hinder their membrane permeability. The invention aims to improve the efficiency of nucleic acid delivery, a critical aspect in drug delivery research.

Background research highlights the limitations of earlier polymer-based vectors such as naturally occurring polymers like poly(lysine) and chitosan, which had poor transfection efficiency and toxicity issues. Synthetic polymers like poly(ethyleneimine) showed better efficiency but similar toxicity problems. Linear PBAEs were developed to mitigate these issues, offering improved biodegradability and biocompatibility, yet the need for more efficient delivery vectors persists.

Innovative Structure of the branched polymers involves at least two different linear PBAE polymers connected via branched linkers. This structure enhances properties such as nucleic acid delivery efficiency compared to linear PBAEs. The polymers of Formula (I) include specific structural components like heteroalkylene linkers and various substituents, which are crucial for their function and performance.

Applications include compositions comprising the branched polymers, potentially in combination with excipients. These compositions can be used for delivering agents to cells or subjects, offering therapeutic benefits in treating or preventing diseases. The invention also provides kits containing the compositions and instructions for their use, broadening the potential for practical applications in medical treatments.

Government Support for this invention was provided by the National Institutes of Health and the Defense Health Agency, indicating its significance and potential impact in the field of medical research and development. The invention's features, objects, and advantages are further detailed in the complete description, offering insights into its potential applications and benefits.