George Church

A method of altering a eukaryotic cell is provided including transfecting the eukaryotic cell with a nucleic acid encoding RNA complementary to genomic DNA of the eukaryotic cell, transfecting the eukaryotic cell with a nucleic acid encoding an enzyme that interacts with the RNA and cleaves the genomic DNA in a site specific manner, wherein the cell expresses the RNA and the enzyme, the RNA binds to complementary genomic DNA and the enzyme cleaves the genomic DNA in a site specific manner.

Background The Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction of genetic variant impact, particularly where relevant to disease. The fve complete editions of the CAGI community experiment comprised 50 challenges, in which participants made blind predictions of phenotypes from genetic data, and these were evaluated by independent assessors. Results Performance was particularly strong for clinical pathogenic variants, including some difcult-to-diagnose cases, and extends to interpretation of cancer-related variants. Missense variant interpretation methods were able to estimate biochemical efects with increasing accuracy. Assessment of methods for regulatory variants and complex trait disease risk was less defnitive and indicates performance potentially suitable for auxiliary use in the clinic. Conclusions Results show that while current methods are imperfect, they have major utility for research and clinical applications. Emerging methods and increasingly la

The invention generally relates to methods for maintaining the integrity and identification of a nucleic acid template in a multiplex sequencing reaction. In certain embodiments, methods of the invention involve obtaining a template nucleic acid, incorporating a pair of sequence identifiers into the template, and sequencing the template.

A method for the systemic delivery of a polypeptide within a subject is provided by creating genetically modified skin cells via topical introduction of a genetically engineered virus which delivers a nucleic acid encoding a therapeutic polypeptide for expression by the skin cells, wherein the expressed therapeutic polypeptide is secreted by the skin cells and is introduced into the circulatory system of the subject.

Methods making and using genomically recoded cells or organisms are provided including genomically recoded cells or organisms that lack the ability to translate a foreign nucleic acid sequence into a polypeptide that may be toxic to the genomically recoded cell or organism.

DNA-PAINT combined with total Internal Reflection Fluorescence (TIRF) microscopy enables the highest localization precisions, down to single nanometers in thin biological samples, due to TIRF's unique method for optical sectioning and attaining high contrast. However, most cellular targets elude the accessible TIRF range close to the cover glass and thus require alternative imaging conditions, affecting resolution and image quality. Here, we address this limitation by applying ultrathin physical cryosectioning in combination with DNA-PAINT. With "tomographic & kinetically-enhanced" DNA-PAINT (tokPAINT), we demonstrate the imaging of nuclear proteins with sub-3 nanometer localization precision, advancing the quantitative study of nuclear organization within fixed cells and mouse tissues at the level of single antibodies. We believe that ultrathin sectioning combined with the versatility and multiplexing capabilities of DNA-PAINT will be a powerful addition to the toolbox of quantitative DNA-based super-resolution microscopy in intracellular structural analyses of proteins, RNA and DNA in situ.

2023-09-26 Assigned to PRESIDENT AND FELLOWS OF HARVARD COLLEGE reassignment PRESIDENT AND FELLOWS OF HARVARD COLLEGE ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CHAN, Ying Kai, CHURCH, GEORGE

Cyanobacteria are explored as phototrophic cell factories for the conversion of CO2 to chemicals. Although several cyanobacterial platforms have been established, discovering novel cyanobacterial strains with different growth and metabolic traits would be advantageous. Here, we describe de novo genome assembly and pan-genome analysis of eight fast-growing Indian isolates of Synechococcus elongatus, displaying an average doubling time of 3-4 h. The draft genome sequences of S. elongatus PCC 11801 and PCC 11802 were earlier reported by our group. However, here we present circular un-gapped genome sequences of all the eight strains. Their pan-genome analysis showed that these strains form a distinct sub-clade within the S. elongatus clade, and are closely related to a widely used cyanobacterium S. elongatus PCC 7942. Pan-genome and extra-chromosomal DNA sequence analyses further …