Engineered viral particles for targeted delivery

Engineered viral particles using Chandipura, Perinet, or Jurona virus glycoproteins with targeted delivery moieties and mutations address the issues of non-specific transduction and complement sensitivity, providing stable and efficient delivery to immune cells.

WO2026107131A2 Publication Date: 2026-05-21ORBITAL THERAPEUTICS INC
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Patent Information

Application Number
PCT/US2025/055240
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Priority Date
2024-11-14
Filing Date
2025-11-13
Publication Date
2026-05-21

AI Technical Summary

Technical Problem

Existing viral vectors, such as those using Vesicular Stomatitis Virus (VSV)-derived glycoproteins, exhibit broad tropism leading to non-specific cell transduction and off-target effects, particularly in cells with low LDL-R expression like immune cells, and are sensitive to serum complement inactivation.

Method used

Engineering viral particles with glycoproteins from Chandipura, Perinet, or Jurona viruses that naturally do not bind human cell receptors, combined with targeted delivery moieties and specific mutations like I347N, I347Q, R354G, and R354N, to enhance targeted delivery to immune cells while reducing off-target effects and complement sensitivity.

Benefits of technology

The engineered viral particles achieve stable, high-titer production, safe, and specific delivery to target cells like T cells with reduced off-target effects and complement inactivation, enabling effective therapeutic nucleic acid delivery.

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Abstract

Provided herein, among other things, are novel and improved glycoproteins, including modified glycoproteins; engineered viral particles comprising such novel and modified glycoproteins; and methods for targeted delivery, for example, to immune cells such as T cells. In some aspects, the engineered viral particles allow targeted delivery of the cargo for various applications, including treating various conditions such as autoimmune diseases and cancer. In some aspects, the engineered viral particles comprise a viral fusogen that is a glycoprotein of Chandipura, Perinet, Piry, Jurona viruses, or variants thereof. In other aspects, the engineered viral particles comprise a modified vesiculovirus glycoprotein mutant, for example, with mutations at amino acids corresponding to positions I347 or R354 of Vesicular Stomatitis Virus G (VSV-G) that reduce binding to Low Density Lipoprotein Receptor (LDL-R).
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