US 2025/0027111 A1 · TEMPERATURE-BASED TRANSIENT DELIVERY OF NUCLEIC ACIDS AND PROTEINS TO CELLS AND TISSUES

Abstract

The present disclosure relates to methods for transiently activating temperature-sensitive agents in one or more cells, for example by contacting one or more cells with a temperature-sensitive agent and transiently incubating the cells at a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. Additionally, the present disclosure relates to methods of contacting one or more cells in a subject with a temperature-sensitive agent and then lowering the subject's core body temperature to a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. The disclosure also relates to methods of contacting one or more cells in a subject with a temperature-sensitive agent, maintaining the subject's surface body temperature at a permissive temperature for inducing an activity of the temperature-sensitive agent in the cells. Further disclosed are methods of treating a subject with a temperature-sensitive therapeutic agent.

Claims20

Dependent claims

A method for expressing a protein in a mammalian subject, comprising:

administering an effective amount of a composition to the mammalian subject by intradermal injection to express the protein in the mammalian subject,
wherein the composition comprises an excipient and a temperature-sensitive agent (ts-agent),
wherein the ts-agent is a temperature-sensitive self-replicating RNA encoding the protein and comprising a viral replicon lacking a viral structural protein coding region,
wherein the RNA is not packaged in a viral particle,
wherein the ts-agent is capable of expressing the protein at a higher level at a permissive temperature from 31° C. to 35° C. than at a non-permissive temperate of 37° C.±0.5° C., and
wherein the protein is heterologous to the viral replicon.

3 more elements

Dependencies are inferred from the claim text.

Temperature-based transient delivery of nucleic acids and proteins to cells and tissues

Life of this patent

Temperature-based transient delivery of nucleic acids and proteins to cells and tissues

Life of this patent

Abstract

Claims20