Sensing of pathogens’ components is a fundamental cellular immune response. Pathogens have therefore evolved strategies to evade such cellular immune responses. KSHV LANA is a multifunctional protein and plays an essential role in maintaining the latent infection by tethering viral genomic DNA to the host chromosome. We adopted the inducible protein knockdown approach and found that depletion of LANA induced rapid degradation of viral genomic DNA, which is mediated by innate immune DNA sensors and autophagy pathway. These observations suggest that LANA may play a role in hiding KSHV episome from innate immune DNA sensors. Our study thus provides new insights into the role of LANA in latency maintenance.

2023-08-01·Current opinion in virology

Kaposi sarcoma-associated herpesvirus latency-associated nuclear antigen: more than a key mediator of viral persistence.

Review

作者: Stein, Saskia C ; Schulz, Thomas F ; Freise, Anika

Kaposi sarcoma-associated herpesvirus (KSHV), or human herpesvirus-8, is an oncogenic herpesvirus. Its latency-associated nuclear antigen (LANA) is essential for the persistence of KSHV in latently infected cells. LANA mediates replication of the latent viral genome during the S phase of a dividing cell and partitions episomes to daughter cells by attaching them to mitotic chromosomes. It also mediates the establishment of latency in newly infected cells through epigenetic mechanisms and suppresses the activation of the productive replication cycle. Furthermore, LANA promotes the proliferation of infected cell by acting as a transcriptional regulator and by modulating the cellular proteome through the recruitment of several cellular ubiquitin ligases. Finally, LANA interferes with the innate and adaptive immune system to facilitate the immune escape of infected cells.

2021-03-01·Molecular Pharmaceutics2区 · 医学

Peptide/Lipid-Associated Nucleic Acids (PLANAs) as a Multicomponent siRNA Delivery System

2区 · 医学

Article

作者: Hall, Ryley ; Mozaffari, Saghar ; Mahdipoor, Parvin ; Montazeri Aliabadi, Hamidreza ; Alasmari, Abdulaziz ; Parang, Keykavous

RNAi is a biological process that utilizes small interfering RNA (siRNA) to prevent the translation of mRNA to protein. This mechanism could be beneficial in preventing the overexpression of proteins in cancer. However, the cellular delivery of siRNA has proven to be challenging due to its inherent negative charge and relative instability. Here, we designed a multicomponent delivery system composed of a specifically designed peptide (linear or cyclic fatty acyl peptide conjugates and hybrid cyclic/linear peptides) and several lipids (DOTAP, DOPE, cholesterol, and phosphatidylcholine) to form a nanoparticle, which we have termed as peptide lipid-associated nucleic acids (PLANAs). Five formulations were prepared (a formulation with no peptide, which was named lipid-associated nucleic acid or LANA, and PLANA formulations A-D) using a mini extruder to form uniform nanoparticles around 100 nm in size with a slightly positive charge (less than +10 mv). Formulations were evaluated for peptide incorporation, siRNA encapsulation efficiency, release profile, toxicity, cellular uptake, and protein silencing. Our experiments showed effective encapsulation of siRNA (>95%), a controlled release profile, and negligible toxicity in formulations that did not contain a positively charged lipid. The results also revealed that PLANAs C and D exhibited optimum cellular uptake (with 80-90% siRNA-positive cells for most of the formulations). PLANA D formulation was selected to silence two model proteins (Src and RPS6KA5) in the triple-negative human breast cancer cell line MDA-MB-231, with promising silencing efficiency, which diminished the expression of RPS6KA5 and Src to approximately 29 and 38% compared to naïve cells, respectively. Many approaches have been investigated for safe and efficient delivery of nucleic acids in the last 20 years; however, many have failed due to the multifaceted challenges to overcome. Our results show a promising potential for a multicomponent design that incorporates different components for a variety of delivery tasks, which warrants further investigation of PLANAs in vivo.

项与 LANA-PL 相关的新闻（医药）

2024-01-12

·PRNewswire

KIND and Lana Condor Invite Americans to Quit the New Year's Resolutions that No Longer Serve Them

By Launching Faux Wellness Store 'Better You by Lana,' KIND Empowers Consumers to Reimagine How We Start the Year NEW YORK, Jan. 12, 2024 /PRNewswire/ -- Today on Quitter's Day, KIND Snacks is announcing Better You by Lana, a one-day-only immersive wellness pop-up based in Los Angeles, California, that flips the script on how to start the New Year, with actress, Lana Condor. By launching on Quitter's Day, the day by which most Americans have quit their New Year's resolutions, KIND and Lana are inviting consumers to shut out the noise and stress that heightens around the New Year and trust their taste buds. Continue Reading Better You By Lana Pop-up Experience Better You By Lana Pop-up Experience Health and diet-related New Year's resolutions rank among the highest set during the New Year. The pressure to "be better" at the start of each year is often matched with confusion. One recent study on eating habits showed that while over 70% of respondents across markets want to be healthier, half of the group found difficulty understanding what they need to do when it comes to making choices about their health1. The abundance of noise and confusion creates conflicting messaging around how and what people should eat. Through the pop-up experience and partnership with Lana, KIND invites Americans to think differently about the pressures we face when making choices about food and wellness. "It is nearly impossible to start the year without the overwhelming pressure and noise of our 'eat this, not that' culture that escalates each January," said Osher Hoberman, Chief Marketing Officer at KIND. "As a continuation of KIND's commitment to nutrition education and nourishment, we are challenging the status quo and empowering Americans to trust their taste buds to lead them to whole, recommended foods we're not eating enough of today." "Each and every January, we all feel like we should be changing our daily routines to become better versions of ourselves. It's time to ask ourselves how well these resolutions are serving us," said Lana. "Better You by Lana certainly sounds like a wellness store in name, but the experience KIND and I teamed up to create is anything but. We will empower consumers to shut out the noise that comes with the new year." To visit Better You by Lana, stop by Santa Monica Place, Unit 146 from 12–9 pm PT in Santa Monica, California. The first 100 people in line will receive a custom gift from Lana and KIND while supplies last. About KIND Snacks Since 2004, KIND has been on a mission to create a kinder and healthier world – one snack and one act at a time. Its iconic KIND® bars – made with real, recognizable ingredients – sparked the growth of an entirely new healthy snacking category. Today, KIND has a family of more than 80 snacks that offer solutions for a variety of occasions. All of KIND's products lead with a nutrient-dense first ingredient –nuts or whole grains – and do not contain genetically engineered ingredients, sugar alcohols or artificial sweeteners. Inspired by the belief that acts of kindness can be a transformative force for good, the KIND brand seeks to inspire kindness and empathy. KIND was founded by Daniel Lubetzky. To learn more about KIND, please visit and join us on LinkedIn, Instagram, TikTok and YouTube. 1 Grimmelt, A., Moulton, J., Pandya, C., & Snezhkova, N. (2022, October 5). Hungry and confused: The winding road to conscious eating. McKinsey & Co. SOURCE KIND Healthy Snacks

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适应症	最高研发状态	国家/地区	公司	日期
哮喘	临床前	-	康龙化成（北京）新药技术股份有限公司	-
肺性高血压	临床前	-	康龙化成（北京）新药技术股份有限公司	-
慢性阻塞性肺疾病	临床前	-	康龙化成（北京）新药技术股份有限公司	-