公开(公告)号：US11959127B2

公开(公告)日：2024-04-16

申请号：US17204782

申请日：2021-03-17

Applicant: CALIFORNIA INSTITUTE OF TECHNOLOGY

Inventor： Mikhail G. Shapiro ,  Dan Piraner ,  Mohamad H. Abedi ,  Brittany Moser ,  Audrey Lee-Gosselin

IPC: C12Q1/68 ,  B01L7/00 ,  C12N15/10 ,  C12N15/63 ,  C12N15/82 ,  C12Q1/6825 ,  G01N33/53 ,  C12N15/00

CPC classification number: C12Q1/6825 ,  B01L7/52 ,  C12N15/1055 ,  C12N15/63 ,  C12N15/8217 ,  G01N33/53 ,  C12N15/00 ,  C12Q2525/30

Abstract: Temperature sensitive transcriptional bioswitches and related genetic circuits and in particular bandpass and/or multiplex genetic circuits, vectors, cells, compositions methods and systems are described.

公开(公告)号：US20230210926A1

公开(公告)日：2023-07-06

申请号：US18066814

申请日：2022-12-15

Applicant: California Institute of Technology

Inventor： Marjorie T. Buss ,  Robert C. Hurt ,  Katie K. Wong ,  Mikhail G. Shapiro ,  Mengtong Duan ,  Arash Farhadi ,  Mei Yi You

IPC: A61K35/748 ,  C07K14/195 ,  A61K49/22 ,  A61P35/00

CPC classification number: A61K35/748 ,  A61K49/22 ,  A61P35/00 ,  C07K14/195 ,  A61K2035/115

Abstract: Disclosed herein include methods, compositions, and kits suitable for use in dynamic non-destructive imaging. The non-destructive imaging can be nonlinear ultrasound imaging. There are provided, in some embodiments, nucleic acid compositions encoding gas vesicles (GVs) capable of producing nonlinear ultrasound contrast upon expression in a prokaryotic cell (e.g., a probiotic bacterial cell) or a eukaryotic cell (e.g., a therapeutic mammalian cell).

公开(公告)号：US11229809B2

公开(公告)日：2022-01-25

申请号：US15912359

申请日：2018-03-05

Applicant: California Institute of Technology

Inventor： David Reza Mittelstein ,  Morteza Gharib ,  Stefanie Heyden ,  Michael Ortiz ,  Mikhail G. Shapiro

IPC: A61N7/00 ,  A61M37/00 ,  A61B8/08 ,  A61B17/3205 ,  A61B5/055 ,  A61B18/00 ,  A61B90/00 ,  A61B17/00

Abstract: Systems and methods for targeting specific cell types by selective application of ultrasonic harmonic excitation at a resonance frequency (“oncotripsy”) for the specific cell types are presented. The systems and the methods result in permeabilization, lysis, and/or death of the targeted specific cell types by using ultrasonic harmonic excitations that have a frequency and a pulse duration specifically tuned to disrupt nuclear membranes of the targeted specific cell types by inducing a destructive vibrational response therein while leaving non-targeted cell types intact. Target cells may be neoplastic.

公开(公告)号：US11118210B2

公开(公告)日：2021-09-14

申请号：US15663635

申请日：2017-07-28

Applicant: CALIFORNIA INSTITUTE OF TECHNOLOGY

Inventor： Raymond W. Bourdeau ,  Anupama Lakshmanan ,  Arash Farhadi ,  Mikhail G. Shapiro ,  Audrey Lee-Gosselin

IPC: C12Q1/10 ,  A61K49/22 ,  A61K49/18 ,  C12N15/74 ,  C07K14/32 ,  C12N15/70 ,  C07K14/195

Abstract: Hybrid gas vesicle gene cluster (GVGC) configured for expression in a prokaryotic host are described comprising gas vesicle assembly (GVA) genes native to a GVA prokaryotic species and capable of being expressed in a functional form in the prokaryotic host, and one or more gas vesicle structural (GVS) genes native to one or more GVS prokaryotic species, at least one of the one or more GVS prokaryotic species different from the GVA prokaryotic species, and related gas vesicle reporting (GVR) genetic circuits, genetic, vectors, engineered cells, and related compositions methods and systems to produce GVs, hybrid GVGC and/or image a target site.

公开(公告)号：US10955496B2

公开(公告)日：2021-03-23

申请号：US15663600

申请日：2017-07-28

Applicant: CALIFORNIA INSTITUTE OF TECHNOLOGY

Inventor： George J. Lu ,  Mikhail G. Shapiro ,  Arash Farhadi ,  Jerzy O. Szablowski

IPC: G01R33/28 ,  A61B5/055 ,  G01R33/50 ,  A61B8/08 ,  G01R33/48 ,  G01R33/56 ,  A61B8/00

Abstract: Gas vesicle protein structures and related compositions, methods, and systems for singleplexed and/or multiplexed magnetic resonance imaging of a target site alone or in combination with ultrasound are described, in which the gas vesicle protein structures provide contrast for the imaging.

公开(公告)号：US12209268B2

公开(公告)日：2025-01-28

申请号：US17334953

申请日：2021-05-31

Applicant: CALIFORNIA INSTITUTE OF TECHNOLOGY

Inventor： Raymond W. Bourdeau ,  Anupama Lakshmanan ,  Arash Farhadi ,  Mikhail G. Shapiro ,  Audrey Lee-Gosselin

IPC: C12N15/75 ,  A61K49/18 ,  A61K49/22 ,  C07K14/195 ,  C07K14/32 ,  C12N15/70 ,  C12N15/74 ,  C12Q1/10

Abstract: Hybrid gas vesicle gene cluster (GVGC) configured for expression in a prokaryotic host are described comprising gas vesicle assembly (GVA) genes native to a GVA prokaryotic species and capable of being expressed in a functional form in the prokaryotic host, and one or more gas vesicle structural (GVS) genes native to one or more GVS prokaryotic species, at least one of the one or more GVS prokaryotic species different from the GVA prokaryotic species, and related gas vesicle reporting (GVR) genetic circuits, genetic, vectors, engineered cells, and related compositions methods and systems to produce GVs, hybrid GVGC and/or image a target site.

公开(公告)号：US20230047753A1

公开(公告)日：2023-02-16

申请号：US17814384

申请日：2022-07-22

Applicant: California Institute of Technology

Inventor： Jerzy O. Szablowski ,  Hongyi Li ,  John E. Heath ,  Mikhail G. Shapiro

IPC: C12N15/861

Abstract: Disclosed herein include adeno-associated virus (AAV) acoustic targeting peptides. An AAV comprising the AAV acoustic targeting peptide can exhibit increased transduction at site(s) of focused ultrasound blood-brain barrier opening (FUS-BBBO), increased neuronal tropism, and diminished transduction of peripheral organs. Disclosed herein include recombinant adeno-associated virus (rAAV) comprising an AAV acoustic targeting peptide disclosed herein. Also provided herein include methods of delivering an agent to one or more target brain region(s) of a subject.

公开(公告)号：US20230016245A1

公开(公告)日：2023-01-19

申请号：US17866240

申请日：2022-07-15

Applicant: California Institute of Technology

Inventor： Mengtong Duan ,  Mikhail G. Shapiro

IPC: C12N15/85 ,  A61K49/22

Abstract: Disclosed herein include methods, compositions, and kits enabling expression of multiple proteins from a single mRNA with a predetermined stoichiometry. There are provided, in some embodiments, nucleic acid compositions comprising a promoter operably linked to a polynucleotide comprising a first nucleic acid unit encoding first unit payload protein(s) and a second nucleic acid unit encoding second unit payload protein(s). The first nucleic acid unit and the second nucleic acid unit can each comprise a 3′ engineered translation initiation site (eTIS) comprising a three-nucleotide tunable element immediately upstream of a start codon. The eTIS of each of the first nucleic acid unit and the second nucleic acid unit can be configured to achieve a predetermined stoichiometry of the first unit payload protein(s) and the second unit payload protein(s) in a cell or cell-like environment.

公开(公告)号：US20230173489A1

公开(公告)日：2023-06-08

申请号：US18073102

申请日：2022-12-01

Applicant: California Institute of Technology

Inventor： Di Wu ,  Mikhail G. Shapiro

IPC: B01L3/00 ,  C12N1/20 ,  C12N5/071 ,  C12N15/85 ,  C12N15/70

CPC classification number: B01L3/502761 ,  C12N1/20 ,  C12N5/0686 ,  C12N15/70 ,  C12N15/85 ,  B01L2200/0652 ,  B01L2300/0654 ,  B01L2400/0436 ,  C12N2800/10

Abstract: Disclosed herein include methods, compositions, and kits suitable for use in sorting a population of cells. In some embodiments, the method comprises flowing a fluid sample comprising a population of cells through a microfluidic channel. The population of cells can be configured to express gas vesicles (GVs) in a context-dependent manner. The expression of GVs within a cell can increase the compressibility (β) and reduce the density (ρ) of said cell, thereby modulating the acoustic contrast (Φ) of said cell relative to the fluid in the microfluidic channel. The method can comprise applying ultrasound to the microfluidic channel. Applying ultrasound can generate acoustic standing wave(s) in the microfluidic channel, thereby positioning pressure antinode(s) in the microfluidic channel.

公开(公告)号：US20230094152A1

公开(公告)日：2023-03-30

申请号：US17936286

申请日：2022-09-28

Applicant: California Institute of Technology

Inventor： Shirin Shivaei ,  Mikhail G. Shapiro

IPC: C12N15/86 ,  C12N15/63 ,  A61B8/08

Abstract: Disclosed herein include methods, compositions, and kits suitable for use in imaging of in situ gene expression. There are provided, in some embodiments, viral vector compositions. Disclosed herein includes a single viral vector comprising one or more gas vesicle assembly (GVA) gene(s) encoding one or more GVA protein(s), and one or more gas vesicle structural (GVS) gene(s) encoding one or more GVS protein(s). The one or more GVA protein(s) and the one or more GVS protein(s) can be capable of forming gas vesicles (GVs) upon expression in a cell.