Methods of using ZSCAN4 for rejuvenating human cells

Inventors

Ko, Minoru S. H.

Assignees

Elixirgen Therapeutics Inc

Abstract

The present disclosure relates to methods for increasing telomere length in one or more human adult cells and/or increasing genome stability of one or more human adult cells, for example by contacting one or more human adult cells with an agent that increases expression of Zscan4 in the one or more human adult cells. Methods of treating a subject in need of telomere lengthening, treating a disease or condition associated with a telomere abnormality, of rejuvenating one or more human adult cells, of rejuvenating tissues or organs, and of rejuvenating a subject in need thereof, for example by contacting one or more human adult cells in the subject with an agent that increases expression of Zscan4, or by administering to a subject in need thereof, an agent that increases expression of Zscan4 is also provided.

Core Innovation

The disclosure relates to methods of increasing telomere length and improving genome stability in human adult non-embryonic cells by increasing ZSCAN4 expression. It identifies Zscan4 as an upstream effector for telomere elongation in human adult cells, including human fibroblasts, and emphasizes an unexpected rapid telomere elongation phenotype upon Zscan4 overexpression in human fibroblasts.

Human fibroblasts show rapid telomere elongation after Zscan4 overexpression, with normal fibroblasts exhibiting an increase in telomere length and Fanconi anemia fibroblasts exhibiting a larger increase. The disclosure links introduction of Zscan4-modulating compositions to telomere lengthening and supports Zscan4-mediated telomere elongation in human adult cell contexts.

The disclosed approaches include increasing Zscan4 via Zscan4-encoding nucleic acids, Zscan4 proteins, and Zscan4-inducing agents. The nucleic acid delivery formats explicitly described include synthetic mRNA and Sendai virus vectors carrying an isolated nucleic acid molecule encoding human Zscan4, and the disclosure also states therapeutic uses including treating telomere-abnormality diseases, rejuvenating cells, tissues, and organs, and engrafting treated bone marrow cells.

Claims Coverage

The provided set includes two independent claims. Across these claims, the main inventive features focus on introducing in vitro an isolated nucleic acid molecule encoding human Zscan4 into human bone marrow or blood cells, inducing telomere lengthening, restricting the nucleic acid to synthetic mRNA or a Sendai virus vector, and engrafting modified cells in subjects with Fanconi anemia or dyskeratosis congenita.

The independent claims collectively cover inducing telomere lengthening in patient-derived human bone marrow or blood cells via in vitro introduction of an isolated nucleic acid molecule encoding human Zscan4, with the nucleic acid comprised in a synthetic mRNA or a Sendai virus vector. The second independent claim further requires engrafting of the Zscan4-induced, telomere-lengthened cells into patients with Fanconi anemia or dyskeratosis congenita.

Stated Advantages

Documented Applications