Systems for activating and expanding cell populations are useful for several applications. For example, mesenchymal stem cells (MSCs) are useful for tissue engineering, B cells for antibody production, non-mammalian cells for small molecule production and immune cells for re-infusion via adoptive immunotherapy. A current manufacturing bottleneck is the safe and rapid proliferation of cells. Accordingly, new compositions and methods to expand target cell populations are needed. UC Berkeley researchers have developed a platform for the expansion and proliferation of cells by using a 2D hydrogel scaffold with tunable mechanics and incorporated streptavidin moieties. The system was validated by expanding human T cells and showed T cell expansion 41% and 70% greater than the current clinical standard. This greater fold expansion was preceded by increased metabolic and proliferation-related transcriptional activity.

IS110 family transposons encode a protein component (also referred to as the transposase) and a non coding RNA component (also referred to as the bridgeRNA or bRNA). In its naturally occurring context, a bRNA-bound transposase directs the integration of its cognate transposon (also referred to as the donor) into target DNA sites. The nucleic acid sequence and structure of the bRNA partially determines the sequence identify of the terminal ends of the mobilized donor, and the sequence identify of the target DNA molecule (also referred to as the target or target DNA). UC Berkeley researchers have developed a programmable gene editing technology based on IS110 family transposons that can be used for targeted insertions, deletions, excisions, inversions, replacements, and capture of DNA in vitro and in vivo. Additionally, this technology can be multiplexed to achieve complex assembles of multiple fragments of DNA.

Efficient delivery and expression of exogenous proteins in cell populations (e.g., cells in the body) for gene therapy / gene editing applications, is an important goal in biomedicine. This can be hampered by inefficient transport of enzymes from outside the body to cells within the body. When delivering nucleic acids or proteins of interest (e.g., DNA editing enzymes), most delivery methods can only reach and enter a small subset of cells within a tissue. There is a need for compositions and methods for improved delivery of proteins of interest, and such is provided herein. UC Berkeley researchers have discovered that delivery of a molecular cargo to a target cell can be more efficiently achieved by using a cell as the delivery vehicle. This can be accomplished by delivering a nucleic acid encoding an enveloped delivery vehicle (EDV) (one that comprises a molecular cargo), to a producer cell where the producer cell produces the EDV and thereby delivers the molecular cargo to neighboring cells (referred to herein as receiver cells). Thus, there is no human intervention between delivery of a subject nucleic acid (encoding the EDV) and subsequent delivery of EDVs to target cells (receiver cells).  

A revolutionary handheld force and load sensing device designed to measure and alert surgeons of critical force thresholds during surgical device deployment during flexible ureteroscopy, enhancing patient safety and surgical outcomes.

Solid lipid nanoparticles are useful for delivering mRNA, and have potential to treat a wide variety of diseases. SLNs contain a PEGylated lipid, which is generally in the 1-5% range and is needed to maintain SLN stability, size, tissue diffusion and lower toxicity. However, excessive PEGylation also results in lower cell uptake and endosomal disruption. This paradox has limited the efficacy of SLNs, and is termed the “PEG dilemma”. Acid degradable PEGlipidshave great potential for overcoming the PEG dilemma, but have been challenging to develop due to the synthetic challenges associated with working with acetals and their instability at pH 7.4. UC Berkeley researchers have developed a new lipid composed of a self-assembling peptide, an acid degradable lipid and a PEG chain, which can be used to transfect a variety of biomolecules into cells.

Cationic, ionizable lipids are a type of lipid that can switch between neutral and positive charges depending on the pH of their environment. They're crucial in lipid nanoparticle (LNP) formulations, particularly for RNA delivery, where they play a key role in encapsulating and releasing the RNA payload. Unfortunately, conventional chemical de novo synthesis of cationic and ionizable lipids is slow, expensive and inefficient. UC Berkeley researchers have developed compositions and methods of synthesizing cationic, ionizable lipids via standard solid phase peptide synthesis protocols, and integration of (i) the solid phase lipid synthesis, (ii) initial cell screening, and (iii) animal organ or cell targeting in an automated robotic system (ARS).

An innovative imaging system combining X-ray-induced acoustic imaging and CT for enhanced osteoporosis diagnosis.

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