The present disclosure generally relates to therapies involving immune effector cells such as T cells engineered to express antigen receptors such as T cell receptors (TCRs) or chimeric antigen receptors (CARs). It is demonstrated herein that such antigen receptor-engineered immune effector cells may be generated in vitro/ex vivo as well as in vitro by delivering nucleic acid encoding an antigen receptor for genetic modification to cells using particles comprising the nucleic acid and a targeting molecule for targeting the immune effector cells, wherein the targeting molecule is a designed ankyrin repeat protein (DARPin). In particular, DARPins are described herein which are high-affinity binders for CDS binding to the CDS receptor on human and non-human primate (NHP) cells. Nanoparticles functionalized with CD8− targeting DARPins (CDS-DARPin) can deliver genes exclusively and specifically to human CD8.sup.+ T cells in vitro and in vivo.

A modified antisense oligonucleotide of about 10 to about 40 nucleobases is disclosed. The oligonucleotide comprises a targeting sequence having a region complementary to at least one string of three or more identical contiguous nucleobases in a target sequence, wherein the target sequence comprises at least one additional nucleobase compared to the region of the targeting sequence and the at least one additional nucleobase has no complementary nucleobase in the region of the targeting sequence, and wherein the targeting region complementary to the at least one string of three or more identical contiguous nucleobases is internal to the targeting sequence.

The present invention relates to compositions and methods for treating cancer, particularly to agents that inhibit the expression and/or activity of the protein second mitochondria-derived activator of caspase/direct inhibitor of apoptosis-binding protein with low pI (SMAC/Diablo). The inhibiting agents include RNA interference molecules silencing the expression of SMAC/Diablo and peptides modulating its interactions within the cell nucleus and mitochondria. The methods and agents of the present invention are useful in treating cancers associated with overexpression of SMAC/Diablo.

The invention relates to a molecular complex comprising at least one polylysine conjugate (PLL), comprising a main PLL straight chain and at least one molecule F having an average molecular weight of between 50 daltons and 1000 daltons that is covalently bonded to said main chain, and at least one molecule M that is unstable in solution, the conjugate(s) and the molecule(s) M being bonded by means of a non-covalent bond. The invention also relates to a composition comprising a complex of this kind, to a method for obtaining said composition and use thereof, and to the use of one or more PLL-based conjugates for improving the hydrophilicity, the effectiveness, and the activity of a molecule that is unstable in solution, over a time period that is compatible with the use of said molecule. The invention also relates to a method for identifying a PLL-based conjugate or a combination of a plurality of PLL-based conjugates that makes it possible to improve the hydrophilicity, the effectiveness, and the activity of a molecule that is unstable in solution, and to a kit for implementing said method.

The present invention pertains to a ligand that contains a plurality of groups represented by formula (1) and is capable of multivalently binding to a glutamine transporter expressed in excess in a cancer cell compared to a normal cell.

The present invention relates to vaccines comprising at least one mRNA encoding at least one antigen for use in the treatment of a disease in newborns and/or infants, preferably exhibiting an age of not more than 2 years, preferably of not more than 1 year, more preferably of not more than 9 months or even 6 months, wherein the treatment comprises vaccination of the newborn or infant and eliciting an immune response in said newborn or infant. The present invention is furthermore directed to kits and kits of parts comprising such a vaccine and/or its components and to methods applying such a vaccine or kit.

The present disclosure relates to base-editing systems including a fusion protein including a DNA-binding domain and a cytidine deaminase domain and a non-protein uracil-DNA glycosylase inhibitor, and methods of using the same. The DNA-binding domains of base-editing systems of the present disclosure include domains with a variety of target region possibilities, which increase the number and type of sequences that can be edited. The npUGIs of the base-editing systems of the present disclosure improve UDG inhibition (e.g., UDG inhibition is more complete) and are suitable for use in a wide range of organisms.

Peptide-based systems containing hydrophobic amino acids (e.g., tryptophan), charged amino acids (e.g., arginine), and/or sulfur-containing amino acids (e.g., cysteine), which can be used either alone or in combination with nanoparticles (e.g., gold or silver nanoparticles) for siRNA delivery into living cells are disclosed.

Provided are compositions and methods for stabilizing a transfection cocktail containing DNA-cationic polymer complexes for an extended time, while maintaining high transfection efficiency. Such stabilized transfection cocktail can be used to generate transfected cells that can produce, for example, rAAV vectors on a large scale without impacting the key attributes of the virus production, such as, titer, DNA packaged rAAV particle fraction, and rAAV vector purification profile.

Provided herein are compounds comprising cyclic cell penetrating peptides and antisense compounds. Also provided herein are methods of modulating splicing, inhibiting or regulating translation, mediating degradation, blocking expansions of nucleotide repeats, and treating disease using the aforementioned compounds.