Abstract: There are provided herein, inter alia, complexes, compositions and methods for the delivery of nucleic acid into a cell in vivo. The complexes, compositions and methods may facilitate complexation, protection, delivery and release of oligonucleotides and polyanionic cargos into target cells, tissues, and organs both in vitro and in vivo.

Abstract: Antibiotic agents conjugated to a guanidinium-rich molecular transporter (GR-MoTr) are provided. The drug conjugates show surprising increases in efficacy compared to the unconjugated drug in difficult-to-treat bacterial infections including biofilms, stationary and persister cells, and multi-drug resistant bacteria, as well as intracellular bacteria.

Abstract: There are provided herein, inter alia, complexes, compositions and methods for the delivery of therapeutic, diagnostic and imaging agents, including nucleic acid, into a cell. The complexes, compositions and methods may facilitate complexation, protection, delivery and release of oligonucleotides and polyanionic cargos into target cells, tissues, and organs both in vitro and in vivo.

Abstract: There are provided herein, inter alia, complexes, compositions and methods for the delivery of therapeutic, diagnostic and imaging agents, including nucleic acid, into a cell. The complexes, compositions and methods may facilitate complexation, protection, delivery and release of oligonucleotides and polyanionic cargos into lung cells and lung tissue, both in vitro and in vivo.

Abstract: There are provided herein, inter alia, complexes, compositions and methods for a vaccine for COVID-19. The cell-penetrating complexes provided herein may include a nucleic acid non-covalently bound to a cationic amphipathic polymer, the cationic amphipathic polymer including a pH-sensitive immolation domain. The cell-penetrating complexes provided herein are, inter alia, useful in vaccines, wherein the vaccine includes a ribonucleic acid including a sequence encoding a viral protein, a nucleic acid adjuvant and a cationic amphipathic polymer provided herein including embodiments thereof.

Abstract: Methods for preparing a variety of bryostatin compounds are provided. The subject methods provide for preparation of bryostatin 1 in multi-gram quantities in a low and unprecedented number of convergent synthetic steps from commercially available materials. The subject methods are scalable with low estimated material costs and can provide enough material to meet clinical needs. Also provided are a variety of bryostatin analog compounds, and prodrug forms thereof, which are synthetically accessible via the subject methods and pharmaceutical compositions including the same.

Abstract: There are provided herein, inter alia, cationic amphipathic polymers, complexes, and compositions comprising same, and methods for their use including for the delivery of therapeutic, diagnostic and imaging agents, including nucleic acids, into a cell. The complexes, compositions and methods may facilitate delivery and targeted release of the therapeutic, diagnostic and imaging agents to particular cell types and tissues.

Abstract: Antibiotic agents conjugated to a guanidinium-rich molecular transporter (GR-MoTr) are provided. The drug conjugates show surprising increases in efficacy compared to the unconjugated drug in difficult-to-treat bacterial infections including biofilms, stationary and persister cells, and multi-drug resistant bacteria, as well as intracellular bacteria.

Abstract: Methods for preparing a variety of bryostatin compounds are provided. The subject methods provide for preparation of bryostatin 1 in multi-gram quantities in a low and unprecedented number of convergent synthetic steps from commercially available materials. The subject methods are scalable with low estimated material costs and can provide enough material to meet clinical needs. Also provided are a variety of bryostatin analog compounds, and prodrug forms thereof, which are synthetically accessible via the subject methods and pharmaceutical compositions including the same.

Abstract: The design, synthesis, and biological evaluation of a new family of highly effective conjugate compounds, including dendrimeric moieties and branched structures, are described. Pharmaceutical compositions including the subject dendrimeric conjugates and methods of using the same are also provided. Methods of using the subject dendrimeric conjugates include delivering a cargo moiety conjugated to the dendrimeric moieties and branched structures to a cell under suitable conditions. In certain embodiments, the cell is a bacterial cell population, and the subject compounds reduce the bacterial cell population. In certain embodiments of the methods, the subject compound is capable of eradicating one or more of Gram-positive bacteria, mycobacteria, and Gram-negative bacteria. In certain embodiments of the methods, the subject compound is capable of eradicating bacterial biofilms. Methods of using the subject dendrimeric conjugates include treating a subject for a disease or condition.

Abstract: Provided herein is the use of bryostatin agents to selectively enhance expression, translocation and/or cell surface presentation of an antigen in target cells of interest to modulate immunogenicity of the target cells. Aspects of the methods include, administering an effective amount of a bryostatin agent to a subject to modulate immunogenicity of target cells. The subject methods include a method of treating cancer, including administering to a subject an effective amount of a bryostatin agent to enhance cell surface antigen or neoantigen presentation on target cells of the subject, and administering to the subject a therapeutically effective amount of a therapeutic agent that specifically binds the cell surface antigen to treat the subject for cancer. Aspects of the subject methods also include use of the bryostatin agents to sensitize the target cells to clearance by the subject's immune system.

Abstract: There are provided herein, inter alia, cationic amphipathic polymers, complexes, and compositions comprising same, and methods for their use including for the delivery of therapeutic, diagnostic and imaging agents, including nucleic acids, into a cell. The complexes, compositions and methods may facilitate delivery and targeted release of the therapeutic, diagnostic and imaging agents to particular cell types and tissues.

Abstract: There are provided herein, inter alia, complexes, compositions and methods for the delivery of nucleic acid into a cell in vivo. The complexes, compositions and methods may facilitate complexation, protection, delivery and release of oligonucleotides and polyanionic cargos into target cells, tissues, and organs both in vitro and in vivo.

Abstract: Methods for preparing a variety of bryostatin compounds are provided. The subject methods provide for preparation of bryostatin 1 in multi-gram quantities in a low and unprecedented number of convergent synthetic steps from commercially available materials. The subject methods are scalable with low estimated material costs and can provide enough material to meet clinical needs. Also provided are a variety of bryostatin analog compounds, and prodrug forms thereof, which are synthetically accessible via the subject methods and pharmaceutical compositions including the same.

Abstract: Methods for preparing a variety of bryostatin compounds are provided. The subject methods provide for preparation of bryostatin 1 in multi-gram quantities in a low and unprecedented number of convergent synthetic steps from commercially available materials. The subject methods are scalable with low estimated material costs and can provide enough material to meet clinical needs. Also provided are a variety of bryostatin analog compounds, and prodrug forms thereof, which are synthetically accessible via the subject methods and pharmaceutical compositions including the same.

Abstract: Methods for preparing a variety of bryostatin compounds are provided. The subject methods provide for preparation of bryostatin 1 in multi-gram quantities in a low and unprecedented number of convergent synthetic steps from commercially available materials. The subject methods are scalable with low estimated material costs and can provide enough material to meet clinical needs. Also provided are a variety of bryostatin analog compounds, and prodrug forms thereof, which are synthetically accessible via the subject methods and pharmaceutical compositions including the same.

Abstract: Co-oligomer compounds, complexes of the same with polyanions, such as siRNAs, and methods for using the same are provided. the delivery of polynucleotides, into a cell. The subject co-oligomers include at least a liphopilic monomer and at least a hydrophilic monomer (e.g., a guanidinium containing monomer). In some embodiments, the co-oligomer compounds are capable of complexing a siRNA of interest, thereby increasing the cell permeability of the siRNA, prior to release of the siRNA into the cell. In some embodiments, the subject method is a method of delivery a siRNA into a cell. In some embodiments, the subject method is a method of reducing expression of a protein target of a siRNA of interest. The subject co-oligomer/siRNA complexes may be formulated and administered to a subject to treat a condition resulting from expression of a protein target of the siRNA of interest.

Abstract: There are provided herein, inter alia, complexes, compositions and methods for the delivery of therapeutic, diagnostic and imaging agents, including nucleic acid, into a cell. The complexes, compositions and methods may facilitate complexation, protection, delivery and release of oligonucleotides and polyanionic cargos into target cells, tissues, and organs both in vitro and in vivo.

Abstract: The introduction of tools to study, control or expand the inner-workings of algae has been slow to develop. Provided are embodiments of a molecular method based on guanidinium-rich molecular transporters (GR-MoTrs) for bringing molecular cargos into algal cells. The methods of the disclosure have been shown to work in wild-type algae that have an intact cell wall. Developed using Chlamydomonas reinhardtii, this method is also successful with less studied algae, including Neochloris oleoabundans and Scenedesmus dimorphus, thus providing a new and versatile tool for algal research and modification. The method of delivering a cargo compound to an algal cell comprises contacting an algal cell with a guanidinium-rich delivery vehicle comprising a guanidinium-rich molecular transporter (GR-MoTr) linked to a cargo compound desired to be delivered to the algal cell, whereby the guanidinium-rich molecular transporter can traverse the algal cell wall, thereby delivering the cargo compound to the algal cell.

Abstract: The introduction of tools to study, control or expand the inner-workings of algae has been slow to develop. Provided are embodiments of a molecular method based on guanidinium-rich molecular transporters (GR-MoTrs) for bringing molecular cargos into algal cells. The methods of the disclosure have been shown to work in wild-type algae that have an intact cell wall. Developed using Chlamydomonas reinhardtii, this method is also successful with less studied algae, including Neochloris oleoabundans and Scenedesmus dimorphus, thus providing a new and versatile tool for algal research and modification. The method of delivering a cargo compound to an algal cell comprises contacting an algal cell with a guanidinium-rich delivery vehicle comprising a guanidinium-rich molecular transporter (GR-MoTr) linked to a cargo compound desired to be delivered to the algal cell, whereby the guanidinium-rich molecular transporter can traverse the algal cell wall, thereby delivering the cargo compound to the algal cell.