Abstract: In a general aspect, a construction tool can include a template portion arranged in a first plane. The template portion can include a rectangular plate having a slot defined, the slot being angled with respect to an edge of the plate and configured to facilitate marking a cut line on a construction material. The construction tool can also include a base portion arranged in a second plane, the second plane being orthogonal to the first plane. The base portion can include a first portion disposed on a first side of the plate, and a second portion disposed on a second side of the plate of the template portion that is opposite the first side of the plate. The first portion of the base portion can have a first thickness, and the second portion of the base portion having a second thickness that is different than the first thickness.

Abstract: The present invention provides methods for preparing optimized DNA sequences as templates for in vitro transcription of mRNA. These DNA sequences are optimized to avoid premature termination of transcription by RNA polymerase. The invention also provides methods for preparing optimized DNA sequences that include one or more termination signal at their 3? end to reduce or prevent non-templated “runoff” transcription.

Abstract: The present invention provides, among other things, methods for large-scale production of a composition comprising full-length messenger RNA product that is substantially free of double-stranded RNA, and compositions produced using such methods and uses thereof. The present invention is based, in part, on the surprising discovery that mRNA product produced by in vitro transcription using an SP6 RNA polymerase is substantially free of double-stranded RNA. In one aspect, the present invention provides methods of generating large-scale mRNA product for mRNA therapy without need for a chromatography step.

Abstract: The present invention provides, among other things, methods and compositions for selective degradation of proteins. In some aspects, messenger RNAs (mRNAs) are described that encode a ubiquitin pathway moiety and a binding peptide that binds a target protein, wherein the mRNA is encapsulated within a lipid nanoparticle. Also provided herein are mRNAs that encode at least two binding peptides, wherein a first binding peptide binds a ubiquitin pathway moiety and a second binding peptide binds a target protein, and wherein the mRNA is encapsulated within a lipid nanoparticle.