公开(公告)号：US10961513B2

公开(公告)日：2021-03-30

申请号：US15757530

申请日：2016-09-07

Applicant: Massachusetts Institute of Technology

Inventor： Timothy Kuan-Ta Lu ,  Sara da Luz Areosa Cleto

IPC: C12N9/00 ,  C12N15/00 ,  C12N15/82 ,  C07H21/04 ,  C12N15/52 ,  C12N9/24 ,  C12N15/70 ,  C12N15/74

Abstract: Compositions and methods using shufflon recombinases are presented for use in generating genetic diversity in molecules of interest.

公开(公告)号：US10793609B2

公开(公告)日：2020-10-06

申请号：US15579631

申请日：2016-06-03

Applicant: Massachusetts Institute of Technology

Inventor： Timothy Kuan-Ta Lu ,  Sara da Luz Areosa Cleto

IPC: C07K14/245 ,  C12N15/52 ,  C12P21/00 ,  C40B40/06 ,  C12N9/52

Abstract: Provided herein are synthetic pathways from Escherichia coli and Vibrio cholerae genes for the production of new, synthetic nonribosomal peptides, and methods and compositions comprising the same. Some aspects of the present disclosure are directed to modified bacterial cells comprising a compressed biosynthetic pathway that comprises (a) biosynthetic genes obtained from one species encoding enzymes active in the bioassembly of a nonribosomal molecule, (b) biosynthetic genes obtained from another species encoding enzymes active in the bioassembly of a nonribosomal molecule that is different from the nonribosomal molecule of (a). In some embodiments, the biosynthetic genes of (a) are Escherichia coli biosynthetic genes and may include entD gene, an entC gene, an entE gene, an entB gene and an entA gene. In some embodiments, the biosynthetic genes of (b) are Vibrio cholera biosynthetic genes and may include a vibH gene and a vibF gene.

公开(公告)号：US20200063119A1

公开(公告)日：2020-02-27

申请号：US16548143

申请日：2019-08-22

Applicant: Massachusetts Institute of Technology

Inventor： Timothy Kuan-Ta Lu ,  Fahim Farzadfard

IPC: C12N15/10 ,  G16B20/00 ,  G16B40/10 ,  G16B50/20 ,  G16B50/30 ,  G16B50/40 ,  G16B50/50 ,  B01J19/00

Abstract: Provided herein are compositions, systems, and methods for information (e.g., artificial or digital information) recording and storage in nucleic acids (e.g., DNA). Information can be recorded and stored on pre-synthesized storage medium.

公开(公告)号：US10480009B2

公开(公告)日：2019-11-19

申请号：US15283162

申请日：2016-09-30

Applicant: Massachusetts Institute of Technology

Inventor： Timothy Kuan-Ta Lu ,  Nathaniel B. Roquet

IPC: C12N15/63 ,  C12N15/85 ,  G16B30/00 ,  C12N9/16

Abstract: Provided herein are recombinase-based frameworks for building state machines in vitro and in vivo by using chemically controlled DNA excision and inversion operations to encode state in DNA sequence.

公开(公告)号：US20190100769A1

公开(公告)日：2019-04-04

申请号：US15521931

申请日：2015-10-30

Applicant: Massachusetts Institute of Technology

Inventor： Timothy Kuan-Ta Lu ,  Alan Siu Lun Wong ,  Ching Gee Choi

IPC: C12N15/85 ,  C12N15/10 ,  A61K31/55 ,  A61K31/4709

Abstract: Described herein are methods and compositions that enable rapid generation of high-order combinations of genetic elements comprising a CRISPR guide sequence and a scaffold sequence, and a barcode for rapid identification of the combination of genetic elements encoded within a single cell or a pooled population. Also described herein compositions of inhibitors of epigenetic genes and methods for reducing cell proliferation and/or treating cancer.

公开(公告)号：US20180163216A1

公开(公告)日：2018-06-14

申请号：US15580859

申请日：2016-06-10

Applicant: Massachusetts Institute of Technology

Inventor： Timothy Kuan-Ta Lu ,  Mark K. Mimee ,  Christopher Voigt ,  Alex C. Tucker

IPC: C12N15/74 ,  A61K48/00 ,  A61K35/741 ,  C12N15/90 ,  C12N9/12 ,  C12N9/22 ,  C12N9/96 ,  C12N15/11 ,  C12N15/67

CPC classification number: C12N15/74 ,  A61K35/741 ,  A61K48/0066 ,  C07K14/195 ,  C12N9/12 ,  C12N9/16 ,  C12N9/22 ,  C12N9/93 ,  C12N9/96 ,  C12N15/11 ,  C12N15/63 ,  C12N15/67 ,  C12N15/902 ,  C12N2310/14 ,  C12N2310/20 ,  C12N2800/80 ,  C12N2840/203

Abstract: Provided herein, in some aspects, are tools (e.g., methods, compositions and nucleic acids) for building genetic circuits in Bacteroides and Parabacteroides bacteria, as well as the bacteria containing the genetic circuits.

公开(公告)号：US20170369878A1

公开(公告)日：2017-12-28

申请号：US15542670

申请日：2016-01-11

Applicant: Massachusetts Institute of Technology

Inventor： Timothy Kuan-Ta Lu ,  Alan Siu Lun Wong ,  Ching Gee Choi

IPC: C12N15/113 ,  A61K31/7088 ,  A61K31/337 ,  G01N33/50 ,  A61K45/06

CPC classification number: C12N15/113 ,  A61K31/337 ,  A61K31/7088 ,  A61K45/06 ,  C12N15/111 ,  C12N2310/141 ,  C12N2310/51 ,  G01N33/5011

Abstract: Described herein are methods and compositions of combinations of microRNAs that enhance the sensitivity of cancer cells to chemotherapeutic agents or reduce proliferation of cancer cells. Also described herein are methods for the identification of combinations of microRNAs that result in desired effects.

公开(公告)号：US20170255857A1

公开(公告)日：2017-09-07

申请号：US15499202

申请日：2017-04-27

Applicant: Trustees of Boston University ,  Massachusetts Institute of Technology

Inventor： James J. Collins ,  Timothy Kuan-Ta Lu

IPC: G06N3/00 ,  H03M1/74 ,  H03M1/36

CPC classification number: G06N3/002 ,  H03M1/361 ,  H03M1/74

Abstract: Described herein are novel biological converter switches that utilize modular components, such as genetic toggle switches and single invertase memory modules (SIMMs), for converting analog inputs to digital outputs, and digital inputs to analog outputs, in cells and cellular systems. Flexibility in these biological converter switches is provided by combining individual modular components, i.e., SIMMs and genetic toggle switches, together. These biological converter switches can be combined in a variety of network topologies to create circuits that act, for example, as switchboards, and regulate the production of an output product(s) based on the combination and nature of input signals received.

公开(公告)号：US20170183634A1

公开(公告)日：2017-06-29

申请号：US15445700

申请日：2017-02-28

Applicant: Massachusetts Institute of Technology

Inventor： Timothy Kuan-Ta Lu ,  Hiroki Ando ,  Sebastien Lemire

IPC: C12N7/00

CPC classification number: C12N7/00 ,  C12N7/02 ,  C12N15/81 ,  C12N2795/00011 ,  C12N2795/00021

Abstract: Various aspects and embodiments of the invention are directed to high-throughput phage-engineering methods and recombinant bacteriophages with tunable host ranges for controlling phage specificity.

公开(公告)号：US20150087055A1

公开(公告)日：2015-03-26

申请号：US14391817

申请日：2013-04-12

Applicant: MASSACHUSETTS INSTITUTE OF TECHNOLOGY

Inventor： Rahul Sarpeshkar ,  Timothy Kuan-Ta Lu ,  Ramez Danial ,  Jacob Rosenblum Rubens

IPC: G06N3/00

CPC classification number: G06N3/002 ,  B82Y10/00

Abstract: Provided herein are molecular analog gene circuits that exploit positive and negative feedback to implement logarithmically linear sensing, addition, subtraction, and scaling thus enabling multiplicative, ratiometric, and power-law computations. The circuits exhibit Weber's Law behavior as in natural biological systems, operate over a wide dynamic range of up to four orders of magnitude, and can be architected to have tunable transfer functions. The molecular circuits described herein can be composed together to implement higher-order functions that are well-described by both intricate biochemical models and by simple mathematical functions. The molecular circuits described herein enable logarithmically linear analog computation within in-vitro and in-vivo systems with a broad class of molecules, all of which obey the Boltzmann exponential equations of thermodynamics that govern molecular association, attenuation, transformation, and degradation.

Abstract translation: 本文提供了分子模拟基因电路，其利用正反馈来实现对数线性感测，加法，减法和缩放，从而实现乘法，比例和幂律计算。 电路表现出韦伯定律的行为，如在自然生物系统中，在多达四个数量级的宽动态范围内运行，并且可以被设计为具有可调谐的传递函数。 本文描述的分子电路可以组合在一起以实现由复杂的生物化学模型和简单的数学函数所描述的高阶函数。 本文描述的分子电路能够在具有广泛分子类型的体外和体内系统中进行对数线性模拟计算，所有这些分子都遵守支配分子缔合，衰减，转化和降解的热力学的Boltzmann指数方程。