This invention generally relates to a novel RNA composition and its production method useful for generating and expanding induced pluripotent stem cells (iPS cells; iPSC) as well as adult stem cells (ASC). The RNA composition so defined can be used for producing not only non-transgenic but also tumor-free iPS cells. The defined RNA composition contans at least two types of different RNA constructs; one is “miR-302 precursor RNA (pre-miR-302)” and the other is “RNA-dependent RNA polymerase (RdRp)” mRNA. Both of pre-miR-302 and RdRp mRNA contain highly structured RNA comformations, such as hairpin and stem-loop structures. To produce highly structured RNAs, a novel PCR-IVT methodology has been developed and used with a specially designed RNA polymerase-helicase mixture activity.

This invention generally relates to a novel RNA composition and its production method useful for generating and expanding induced pluripotent stem cells (iPS cells; iPSC) as well as adult stem cells (ASC). The RNA composition so defined can be used for producing not only non-transgenic but also tumor-free iPS cells. The defined RNA composition contans at least two types of different RNA constructs; one is “miR-302 precursor RNA (pre-miR-302)” and the other is “RNA-dependent RNA polymerase (RdRp)” mRNA. Both of pre-miR-302 and RdRp mRNA contain highly structured RNA comformations, such as hairpin and stem-loop structures. To produce highly structured RNAs, a novel PCR-IVT methodology has been developed and used with a specially designed RNA polymerase-helicase mixture activity.

Provided methods of using FLT3L-Fc fusion proteins, including doses and dosing regimens and schedules for administering FLT3L-Fc fusion proteins to a subject in need thereof.

Provided methods of using FLT3L-Fc fusion proteins, including doses and dosing regimens and schedules for administering FLT3L-Fc fusion proteins to a subject in need thereof.

The present disclosure relates to bifunctional compounds, which find utility as modulators of enhancer of zeste homolog 2 (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

The present disclosure relates to bifunctional compounds, which find utility as modulators of enhancer of zeste homolog 2 (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

The application is directed to compounds of formulae (IA) and (IB): (IA) and (IB), and their salts and solvates, wherein R.sup.1a, R.sup.2a, .sup.A1, A.sup.2, A.sup.3, A.sup.4, R.sup.1b, R.sup.2b, B.sup.1, B.sup.2, B.sup.3, and G are as set forth in the specification, as well as to methods for their preparation, N pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of, e.g., lysosomal storage diseases, such as Krabbe's disease, and α-synucleinopathies, such as Parkinson's disease.

##STR00001##

The application is directed to compounds of formulae (IA) and (IB): (IA) and (IB), and their salts and solvates, wherein R.sup.1a, R.sup.2a, .sup.A1, A.sup.2, A.sup.3, A.sup.4, R.sup.1b, R.sup.2b, B.sup.1, B.sup.2, B.sup.3, and G are as set forth in the specification, as well as to methods for their preparation, N pharmaceutical compositions comprising the same, and use thereof for the treatment and/or prevention of, e.g., lysosomal storage diseases, such as Krabbe's disease, and α-synucleinopathies, such as Parkinson's disease.

##STR00001##

A therapeutic agent comprising Lon protease, or a variant or active fragment thereof, alpha-hemolysin, or a variant or active fragment thereof, CK1α1, or a variant or active fragment thereof, a c-MYB inhibitor and/or a CEBP-δ inhibitor, for use in therapy, with the proviso that the therapeutic agent does not comprise a bacteria or bacterial supernatant. Methods of production and use thereof.

Aspects of the present disclosure provide compositions comprising NEK10 for example, wild-type NEK10 or a hyper-active NEK10 mutant such as NEK10.sup.S684D, and methods of using such for treating a respiratory disorder such as bronchiectasis.