Lonza Group has filed a patent for a method of reprogramming mammalian somatic cells by regulating the expression of endogenous cellular genes. The method involves using synthetic transcription factors to activate embryonic stem cell-associated genes and suppress somatic cell-specific and cell death-associated genes. The patent also covers therapeutic methods for using the reprogrammed cells for the treatment of diseases amenable to stem cell therapy. GlobalData’s report on Lonza Group gives a 360-degree view of the company including its patenting strategy. Buy the report here.

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According to GlobalData’s company profile on Lonza Group, nanoemulsion cosmetics was a key innovation area identified from patents. Lonza Group's grant share as of September 2023 was 58%. Grant share is based on the ratio of number of grants to total number of patents.

Method for reprogramming mammalian somatic cells using synthetic transcription factors

Source: United States Patent and Trademark Office (USPTO). Credit: Lonza Group Ltd

A recently filed patent (Publication Number: US20230313222A1) describes a method for nuclear reprogramming of mammalian somatic cells. The method involves contacting the somatic cells with a first nucleic acid encoding a guide RNA and a second nucleic acid encoding a transcriptional modulator. The guide RNA binds to the promoter region of an endogenous pluripotency factor gene, while the transcriptional modulator binds to the guide RNA. The transcriptional modulator contains an enzymatically inactive Cas9 polypeptide (dCas9). The somatic cells are then cultured under specific conditions to reprogram them into induced pluripotent stem cells (iPSCs) or transdifferentiate them into a different cell type.

The patent claims cover various aspects of the method. Claim 2 specifies that the reprogramming period can range from 2 to 14 days. Claim 3 states that the method is applicable to human somatic cells, while claim 4 specifies that it can be used with fibroblasts. Claim 5 expands the scope to include primary blood cells, such as peripheral blood mononuclear cells (PBMCs) or cord blood mononuclear cells.

The patent also mentions the selection of pluripotency factor genes, including oct3/4, sox2, klf4, c-myc, lin28, nanog, glis-1, bcl2, and bclx (claim 8). It further describes the fusion of dCas9 with a transcriptional activation domain, such as VP64 or p65 (claim 12). The method can also involve the use of a second synthetic transcription factor that represses the expression of a second pluripotency factor gene (claim 14). The second gene can be p19Arf, p16Ink4a, ROCK, a PKA/PKG/PKC family kinase gene, or genes that inhibit the mTOR pathway when repressed (claim 15).

The patent also covers the use of expression vectors, including non-viral episomal vectors, to deliver the synthetic transcription factors (claim 19). Different combinations of guide RNA and transcriptional modulator can be delivered using separate or combined expression vectors (claims 20 and 21). The method can involve the use of multiple synthetic transcription factors targeting different genes (claim 24). An example of such a combination is dCas9 fused to a transcriptional activation domain, along with guide RNAs targeting the oct3/4, sox2, and klf4 genes (claim 25). The patent also mentions the possibility of using four synthetic transcription factors to activate the expression of four different pluripotency factor genes (claim 26).

Overall, the patent describes a method for nuclear reprogramming of mammalian somatic cells using guide RNA and transcriptional modulators, potentially leading to the generation of induced pluripotent stem cells or transdifferentiation into different cell types. The method can be applied to various types of somatic cells, including human fibroblasts and blood cells. Different combinations of synthetic transcription factors and delivery methods are also covered by the patent claims.

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GlobalData, the leading provider of industry intelligence, provided the underlying data, research, and analysis used to produce this article.

GlobalData Patent Analytics tracks bibliographic data, legal events data, point in time patent ownerships, and backward and forward citations from global patenting offices. Textual analysis and official patent classifications are used to group patents into key thematic areas and link them to specific companies